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CN207040657U - A kind of in vitro low temperature oxygen carrying machine perfusion device of toy liver - Google Patents

A kind of in vitro low temperature oxygen carrying machine perfusion device of toy liver Download PDF

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CN207040657U
CN207040657U CN201720931914.9U CN201720931914U CN207040657U CN 207040657 U CN207040657 U CN 207040657U CN 201720931914 U CN201720931914 U CN 201720931914U CN 207040657 U CN207040657 U CN 207040657U
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oxygenator
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叶啟发
付贞
范林
夏浩洋
程楚红
王彦峰
叶少军
黄伟
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Wuhan University WHU
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Abstract

本实用新型提供一种小动物肝脏离体低温携氧机械灌注装置,包括依次通过肝素涂层管道连通的器官保存装置、离心泵、氧合器、除气泡器、流量控制器、压力传感器;所述氧合器和离心泵之间、氧合器和除气泡器之间分别设置有三通管。本系统通过离心泵提供动力,持续对小动物肝脏进行低温氧合循环灌注,此设备操作简单、灌注路径短、循环设计大大节省灌注液的用量,尤其适应于小动物肝脏低温灌注。

The utility model provides an isolated low-temperature oxygen-carrying mechanical perfusion device for a small animal liver, which comprises an organ preservation device, a centrifugal pump, an oxygenator, a debubbling device, a flow controller, and a pressure sensor that are sequentially connected through a heparin-coated pipeline; A three-way pipe is respectively arranged between the oxygenator and the centrifugal pump, and between the oxygenator and the debubbler. The system is powered by a centrifugal pump to continuously perfuse the liver of small animals with low-temperature oxygenation cycle. This equipment is easy to operate, has a short perfusion path, and the cycle design greatly saves the amount of perfusate. It is especially suitable for low-temperature perfusion of small animal livers.

Description

一种小动物肝脏离体低温携氧机械灌注装置A low-temperature oxygen-carrying mechanical perfusion device for isolated small animal liver

技术领域technical field

本实用新型涉及移植外科供体肝脏的评价与修复领域,尤其涉及一种小动物肝脏离体低温携氧机械灌注装置。The utility model relates to the field of evaluation and repair of transplanted surgical donor livers, in particular to an isolated low-temperature oxygen-carrying mechanical perfusion device for small animal livers.

背景技术Background technique

自21世纪以来,器官移植已成为治疗终末期疾病的最有效手段,器官移植一直被誉为20世纪改变人类生活、生物科学的重大技术。目前,中国的器官移植事业正在迅速发展,这不仅推动了高新技术及相关科学的发展,而且推动了医学伦理学的进步,社会价值观的转变。器官移植始终处于生命科学前沿,其手术复杂程度、难度系数代表着世界医学的一种高精尖技术。然而,器官资源的匮乏严重制约移植事业的进一步发展。Since the 21st century, organ transplantation has become the most effective means of treating terminal diseases. Organ transplantation has always been hailed as a major technology that changed human life and biological science in the 20th century. At present, China's organ transplantation business is developing rapidly, which not only promotes the development of high-tech and related sciences, but also promotes the progress of medical ethics and the transformation of social values. Organ transplantation has always been at the forefront of life sciences, and its complexity and difficulty represent a high-tech technology in world medicine. However, the lack of organ resources seriously restricts the further development of transplantation.

为缓解供体器官资源的短缺矛盾,中国卫生计划委员会与中国红十字会于2010年启动人体器官捐献工作试点,2013年将公民逝世后器官捐献纳入我国移植工作重要议程。同时,由于供肝的短缺,边缘性供肝作为扩大供肝来源的方法,其地位越来越受到人们重视。随着器官灌注液的改进,保存方法及手术技术的提升,边缘供肝的应用逐渐扩大。In order to alleviate the shortage of donor organ resources, the China Health Planning Commission and the Red Cross Society of China launched a pilot project of human organ donation in 2010, and in 2013, organ donation after the death of citizens was included in the important agenda of my country's transplant work. At the same time, due to the shortage of liver donors, the status of marginal liver donors as a way to expand the source of liver donors has attracted more and more attention. With the improvement of organ perfusion fluid, preservation methods and surgical techniques, the application of marginal donor livers has gradually expanded.

然而,临床回顾性研究表明心脏死亡供体(donation after cardiac death,DCD)存在更长时间的热缺血损伤,其移植术后发生肾功能的延迟恢复(delayed graftfunction,DGF)、原发无功能(primary nonfunction, PNF)以及微循环障碍等较脑死亡供体(donation after brain death, DBD)更严重。边缘供肝(脂肪供肝、高龄供肝、肝炎供肝等)所带来的移植术后并发症(PNF、IPF、排斥反应、血管及胆道并发症、HBV复发等)仍是我们面临的严峻挑战。同时,供体器官从获取到移植期间遭受原发疾病、热缺血、冷缺血、冷保存损伤、再灌注损伤等系列因素,供体器官的质量良莠不齐。因此,如何评估、维护供体器官质量、修复损伤是移植事业发展面临的另一个重要挑战,也是当今器官移植领域研究方向之一。However, clinical retrospective studies have shown that donors after cardiac death (donation after cardiac death, DCD) have longer warm ischemic injury, delayed recovery of renal function (delayed graft function, DGF) and primary non-function after transplantation. (primary nonfunction, PNF) and microcirculatory disorders are more serious than those of brain-dead donors (donation after brain death, DBD). Post-transplantation complications (PNF, IPF, rejection, vascular and biliary complications, HBV recurrence, etc.) brought about by marginal donor livers (fatty livers, aged livers, hepatitis donors, etc.) are still a severe problem we face challenge. At the same time, donor organs suffer from primary diseases, warm ischemia, cold ischemia, cold preservation injury, reperfusion injury and other factors during the period from acquisition to transplantation, and the quality of donor organs varies. Therefore, how to assess, maintain the quality of donor organs, and repair damage is another important challenge for the development of transplantation, and it is also one of the research directions in the field of organ transplantation today.

对于边缘供肝,特别是DCD热缺血供肝进行质量评价和功能修复是当前研究热点。本人设计了小动物肝脏低温携氧机械灌注装置,应用低温携氧机械灌注方式进行干预,研究低温携氧机械灌注对供肝的质量进行评价与修复。The quality evaluation and functional restoration of marginal liver donors, especially DCD warm ischemic liver donors, are current research hotspots. I have designed a low-temperature oxygen-carrying mechanical perfusion device for the liver of small animals, and applied the low-temperature oxygen-carrying mechanical perfusion method to intervene, and studied the evaluation and repair of the quality of the donated liver by low-temperature oxygen-carrying mechanical perfusion.

实用新型内容Utility model content

本实用新型的目的是在低温携氧机械灌注系统中对边缘供肝进行修复后使其符合移植需要。The purpose of the utility model is to repair the marginal donor liver in a low-temperature oxygen-carrying mechanical perfusion system so that it meets the needs of transplantation.

本实用新型的目的可以通过以下方式来实现:The purpose of this utility model can be achieved in the following ways:

一种小动物肝脏离体低温携氧机械灌注装置,包括依次通过肝素涂层管道连通的器官保存装置、离心泵、氧合器、除气泡器、流量控制器、压力传感器;所述氧合器和离心泵之间、氧合器和除气泡器之间分别设置有三通管,应用于取样检测实际入肝氧分压。An isolated low-temperature oxygen-carrying mechanical perfusion device for a small animal liver, comprising an organ preservation device, a centrifugal pump, an oxygenator, a debubbler, a flow controller, and a pressure sensor that are sequentially connected through a heparin-coated pipeline; the oxygenator There are three-way pipes between the oxygenator and the centrifugal pump, and between the oxygenator and the debubbler, which are used for sampling and testing the actual partial pressure of oxygen entering the liver.

作为优选项:所述器官保存装置为可分离式结构,包括可分离的内部器官储存盒和外部低温盒;所述器官储存盒上设有门静脉连接件和胆管连接件;所述储存盒底部设有温度控制电路板;同时器官储存盒底部设有温度监测器,温度探针置于器官储存盒应用于实时监测灌注液的温度,自行设置温度以启动预警装置,肝门静脉经门静脉连接件与肝素涂层管道连接构成灌注入口。As a preferred item: the organ preservation device has a detachable structure, including a detachable internal organ storage box and an external low-temperature box; the organ storage box is provided with a portal vein connector and a bile duct connector; There is a temperature control circuit board; at the same time, there is a temperature monitor at the bottom of the organ storage box. The temperature probe is placed in the organ storage box to monitor the temperature of the perfusate in real time, and the temperature can be set by itself to activate the early warning device. The hepatic portal vein connects with heparin through the portal vein. The coated pipe connection forms the filling inlet.

作为优选项:所述门静脉连接件为二通连接件,所述压力传感器与门静脉连接件连接。As a preferred option: the portal vein connection is a two-way connection, and the pressure sensor is connected to the portal vein connection.

作为优选项:还包括胆汁收集装置,所述胆汁收集装置与胆管连接件连通;所述胆管连接件为二通连接件。As a preferred item: a bile collection device is also included, and the bile collection device communicates with the bile duct connection piece; the bile duct connection piece is a two-way connection piece.

作为优选项:所述除气泡器内部为筛网状纤维滤过膜,且其顶部设施有排气孔。As a preferred option: the interior of the debubbler is a mesh-like fibrous filter membrane, and its top is equipped with vent holes.

本实用新型与现有技术相比有如下优点:1.低温携氧机械灌注与冷保存相比较的独特优势在于不仅可以提供营养素给予营养支持、促进体内毒素的排出,而且触发一系列保护机制引起的固有免疫和适应性免疫应答,从而降低缺血再灌注相关的损伤,提高移植物的质量;2.通过保存液携氧的方式对缺血性肝脏提供氧气,以修复ATP的耗损;同时,可在灌注液中添加抗氧化和改善微循环等的药物,对缺血性肝脏进行药物干预治疗;4.此系统中改进了除气泡器的装置,内部为筛网状纤维滤过膜,可以过滤微小血凝块等杂质,不断净化灌注液;5.此系统设备操作简单、灌注路径短、循环设计大大节省灌注液的用量,适应于小动物肝脏低温灌注。Compared with the prior art, the utility model has the following advantages: 1. The unique advantage of low-temperature oxygen-carrying mechanical perfusion compared with cold storage is that it can not only provide nutrients for nutritional support, promote the discharge of toxins in the body, but also trigger a series of protection mechanisms to cause 2. Provide oxygen to the ischemic liver by means of preservation fluid carrying oxygen to repair the consumption of ATP; at the same time, Drugs such as anti-oxidation and improving microcirculation can be added to the perfusion fluid to perform drug intervention treatment on ischemic liver; 4. The device of the air-removing device is improved in this system, and the inside is a mesh-like fiber filter membrane, which can Filter tiny blood clots and other impurities, and continuously purify the perfusate; 5. The equipment of this system is easy to operate, the perfusion path is short, and the cycle design greatly saves the amount of perfusate, which is suitable for low-temperature perfusion of small animal livers.

附图说明Description of drawings

图1为本实用新型结构示意图;Fig. 1 is the structural representation of the utility model;

其中:1为器官保存装置,2为肝素涂层管道,3为离心泵,4和6均为三通管,5为氧合器,7为除气泡器,8为流量控制器,9为压力传感器,10为器官储存盒,11为低温盒,12为胆汁收集装置,门静脉连接件13,胆管连接件14。Among them: 1 is an organ preservation device, 2 is a heparin-coated pipeline, 3 is a centrifugal pump, 4 and 6 are three-way tubes, 5 is an oxygenator, 7 is a debubbling device, 8 is a flow controller, and 9 is a pressure Sensor, 10 is an organ storage box, 11 is a cryogenic box, 12 is a bile collection device, a portal vein connector 13, and a bile duct connector 14.

具体实施方式detailed description

下面结合实施例和附图对本实用新型做进一步说明。Below in conjunction with embodiment and accompanying drawing, the utility model is further described.

一种小动物肝脏离体低温携氧机械灌注装置,包括依次通过肝素涂层管道2连通的器官保存装置1、离心泵3、氧合器5、除气泡器7、流量控制器8、压力传感器9;所述氧合器5和离心泵3之间、氧合器5和除气泡器7之间分别设置有三通管4、6,应用于取样检测实际入肝氧分压。An isolated low-temperature oxygen-carrying mechanical perfusion device for small animal livers, including an organ preservation device 1, a centrifugal pump 3, an oxygenator 5, a debubbler 7, a flow controller 8, and a pressure sensor, which are sequentially connected through a heparin-coated pipeline 2 9. Between the oxygenator 5 and the centrifugal pump 3, and between the oxygenator 5 and the debubbler 7, there are respectively three-way pipes 4 and 6, which are used for sampling and testing the actual partial pressure of oxygen entering the liver.

所述器官保存装置1为可分离式结构,包括可分离的内部器官储存盒10和外部低温盒11;所述器官储存盒10上设有门静脉连接件13和胆管连接件14;所述低温盒11底部设有温度控制电路板;同时器官储存盒10底部设有温度监测器,温度探针置于器官储存盒10应用于实时监测灌注液的温度,自行设置温度以启动预警装置。The organ preservation device 1 is a detachable structure, including a detachable internal organ storage box 10 and an external low-temperature box 11; the organ storage box 10 is provided with a portal vein connecting piece 13 and a bile duct connecting piece 14; the low-temperature box There is a temperature control circuit board at the bottom of 11; at the same time, a temperature monitor is installed at the bottom of organ storage box 10, and the temperature probe is placed in organ storage box 10 to monitor the temperature of the perfusate in real time, and the temperature can be set by itself to activate the early warning device.

所述门静脉连接件13为二通连接件,所述压力传感器9与门静脉连接件连接,肝门静脉经门静脉连接件13与肝素涂层管道连接构成灌注入口。The portal vein connector 13 is a two-way connector, the pressure sensor 9 is connected to the portal vein connector, and the hepatic portal vein is connected to the heparin-coated pipeline through the portal vein connector 13 to form an infusion inlet.

还包括胆汁收集装置12,所述胆汁收集装置12与胆管连接件14连通;所述胆管连接件14为二通连接件,分别与肝脏胆管和胆汁收集装置12连通,胆汁进入胆汁收集装置12。Also includes a bile collection device 12, the bile collection device 12 communicates with the bile duct connector 14;

所述除气泡器7内部为筛网状纤维滤过膜,且其顶部设施有排气孔,灌注液进入除气泡器后,通过内部晒网过滤掉微小血凝块等杂质,灌注液中的气体则通过排气孔排出。The inside of the air-removing device 7 is a screen-like fiber filter membrane, and its top facility has vent holes. After the perfusate enters the air-removing device, impurities such as tiny blood clots are filtered out through the internal drying screen. The gas is exhausted through the exhaust hole.

首先取适量灌注液加入至携氧机械灌注系统中的器官储存盒内,这时连接器官保存装置1、离心泵3之间的灌注管道2,位于器官保存装置1的一端不直接与器官保存装置1连接,而是位于器官储存盒内灌注液液面下方,经离心泵的驱动力,灌注液依次经过氧合器、除气泡器,排除气泡后沿灌注管道回流至器官储存盒,使整个灌注系统管道内充盈灌注液,离心泵停止工作,供体肝脏获取之后,置于4℃器官储存盒内的肝脏灌注液中,胆道通过胆道连接器引出连接至胆汁收集装置,低温盒内放入冰水混合物保持供体肝脏处于低温状态。First, take an appropriate amount of perfusion solution and add it to the organ storage box in the oxygen-carrying mechanical perfusion system. At this time, connect the perfusion pipeline 2 between the organ preservation device 1 and the centrifugal pump 3, and the end of the organ preservation device 1 is not directly connected to the organ preservation device. 1 connection, but located below the liquid level of the perfusate in the organ storage box. Driven by the centrifugal pump, the perfusate passes through the oxygenator and debubbler in sequence, and after removing air bubbles, it flows back to the organ storage box along the perfusion pipeline, so that the entire perfusion The system pipeline is filled with perfusate, and the centrifugal pump stops working. After the donor liver is harvested, it is placed in the liver perfusate in the organ storage box at 4°C. The water mixture keeps the donor liver at a low temperature.

首先启动离心泵,灌注液受离心泵的驱动力,依次经氧合器,除气泡器进入管道系统,整个管道系统内充满灌注液并排出空气后,关闭离心泵,此时将肝门静脉通过门静脉连接器接入灌注管道,再次启动离心泵,灌注液由门静脉开始循环灌注,灌注液流动方向如图中实线粗箭头所示,灌注液经过氧合等过程进入肝脏参与其评价与修复过程,本实用新型使用HTK(histidine-tryptophan-ketoglutarate solution)进行肝脏灌注,离心泵提供动力,氧合器将HTK进行氧合,经管道泵入肝脏,肝静脉流出的HTK经肝外肝素涂层管道回流至离心泵,完成体外循环过程。First start the centrifugal pump, the perfusate is driven by the centrifugal pump, and enters the pipeline system through the oxygenator and debubbler in turn. After the whole pipeline system is filled with perfusate and the air is exhausted, the centrifugal pump is turned off. At this time, the hepatic portal vein passes through the portal vein. The connector is connected to the perfusion pipeline, and the centrifugal pump is started again. The perfusate starts to circulate and perfuse from the portal vein. The flow direction of the perfusate is shown by the thick arrow in the solid line in the figure. The perfusate enters the liver through oxygenation and other processes to participate in its evaluation and repair process. The utility model uses HTK (histidine-tryptophan-ketoglutarate solution) to perfuse the liver, the centrifugal pump provides power, the oxygenator oxygenates the HTK, pumps it into the liver through the pipeline, and the HTK flowing out of the hepatic vein flows back through the extrahepatic heparin-coated pipeline to the centrifugal pump to complete the extracorporeal circulation process.

尽管本说明书较多地使用了 1为器官保存装置,2为肝素涂层管道,3为离心泵,4和6均为三通管,5为氧合器,7为除气泡器,8为流量控制器,9为压力传感器,10为器官储存盒,11为低温盒,12为胆汁收集装置,门静脉连接件13,胆管连接件14等术语,但并不排除使用其他术语的可能性。使用这些术语仅仅是为了更方便的描述本实用新型的本质,把它们解释成任何一种附加的限制都是与本实用新型精神相违背的。Although this manual uses a lot of 1 for organ preservation devices, 2 for heparin-coated pipes, 3 for centrifugal pumps, 4 and 6 are tee tubes, 5 for oxygenators, 7 for debubblers, and 8 for flow rates Controller, 9 is a pressure sensor, 10 is an organ storage box, 11 is a cryogenic box, 12 is a bile collection device, portal vein connector 13, bile duct connector 14 and other terms, but the possibility of using other terms is not excluded. These terms are only used to describe the essence of the utility model more conveniently, and interpreting them as any kind of additional limitation is contrary to the spirit of the utility model.

应当理解的是,本说明书未详细阐述的部分均属于现有技术。It should be understood that the parts not described in detail in this specification belong to the prior art.

应当理解的是,上述针对较佳实施例的描述较为详细,并不能因此而认为是对本实用新型专利保护范围的限制,本领域的普通技术人员在本实用新型的启示下,在不脱离本实用新型权利要求所保护的范围情况下,还可以做出替换或变形,均落入本实用新型的保护范围之内,本实用新型的请求保护范围应以所附权利要求为准。It should be understood that the above-mentioned descriptions for the preferred embodiments are relatively detailed, and cannot therefore be considered as limiting the protection scope of the utility model patent. In the case of the scope of protection of the new claims, replacement or deformation can also be made, all of which fall within the protection scope of the utility model, and the scope of protection of the utility model should be based on the appended claims.

Claims (5)

1.一种小动物肝脏离体低温携氧机械灌注装置,其特征在于:包括通过肝素涂层管道(2)依次连通的器官保存装置(1)、离心泵(3)、氧合器(5)、除气泡器(7)、流量控制器(8)、压力传感器(9);所述氧合器(5)和离心泵(3)之间、氧合器(5)和除气泡器(7)之间分别设置有三通管(4、6)。1. A low-temperature oxygen-carrying mechanical perfusion device for an isolated small animal liver, characterized in that it includes an organ preservation device (1), a centrifugal pump (3), and an oxygenator (5) sequentially connected through a heparin-coated pipeline (2). ), the bubble remover (7), the flow controller (8), the pressure sensor (9); between the oxygenator (5) and the centrifugal pump (3), the oxygenator (5) and the bubble remover ( 7) There are three-way pipes (4, 6) respectively arranged between them. 2.如权利要求1所述的小动物肝脏离体低温携氧机械灌注装置,其特征在于:所述器官保存装置(1)为可分离式结构,包括可分离的内部器官储存盒(10)和外部恒温盒(11);所述器官储存盒(10)上放置有门静脉连接件(13)和胆管连接件(14);所述恒温盒(11)底部设有温度控制电路板;所述器官储存盒(10)上设置有温度探针。2. The small animal liver isolated hypothermic mechanical perfusion device with oxygen carrying device according to claim 1, characterized in that: the organ preservation device (1) is a detachable structure, including a detachable internal organ storage box (10) and an external thermostatic box (11); the organ storage box (10) is placed with a portal vein connector (13) and a bile duct connector (14); the bottom of the thermostatic box (11) is provided with a temperature control circuit board; the A temperature probe is arranged on the organ storage box (10). 3.如权利要求2所述的小动物肝脏离体低温携氧机械灌注装置,其特征在于:所述门静脉连接件(13)为二通连接件,所述压力传感器(9)与门静脉连接件(13)连接。3. The isolated small animal liver low-temperature oxygen-carrying mechanical perfusion device according to claim 2, characterized in that: the portal vein connection (13) is a two-way connection, and the pressure sensor (9) and the portal vein connection (13) CONNECTIONS. 4.如权利要求2所述的小动物肝脏离体低温携氧机械灌注装置,其特征在于:还包括胆汁收集装置(12),所述胆汁收集装置(12)与胆管连接件(14)连通;所述胆管连接件(14)为二通连接件。4. The mechanical perfusion device for isolated small animal liver at low temperature with oxygen according to claim 2, characterized in that it further comprises a bile collection device (12), and the bile collection device (12) communicates with the bile duct connector (14) ; The bile duct connector (14) is a two-way connector. 5.如权利要求1所述的小动物肝脏离体低温携氧机械灌注装置,其特征在于:所述除气泡器(7)内部为筛网状纤维滤过膜,且其顶部设施有排气孔。5. The low-temperature oxygen-carrying mechanical perfusion device for isolated small animal livers according to claim 1, characterized in that: the interior of the debubbler (7) is a mesh-like fiber filter membrane, and the top facility has an exhaust hole.
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Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108432743A (en) * 2018-06-15 2018-08-24 广州军区广州总医院 Portable organ contributes donor machine perfusion system
CN109526944A (en) * 2019-01-07 2019-03-29 成都泰盟软件有限公司 A kind of exhaust bubble structure in Perfused isolated heart system
CN110669669A (en) * 2019-11-05 2020-01-10 西安交通大学医学院第一附属医院 A modular three-dimensional perfusion cell culture system
CN111480644A (en) * 2019-01-27 2020-08-04 宋红丽 Normal-temperature mechanical perfusion combined with gene modification for repairing small animal organ system by stem cells
CN112772638A (en) * 2021-02-24 2021-05-11 吉林大学第一医院 Small animal mechanical perfusion liver temperature control device

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108432743A (en) * 2018-06-15 2018-08-24 广州军区广州总医院 Portable organ contributes donor machine perfusion system
CN108432743B (en) * 2018-06-15 2023-08-11 广东丁沃生医疗器械有限公司 Portable organ donation donor mechanical perfusion system
CN109526944A (en) * 2019-01-07 2019-03-29 成都泰盟软件有限公司 A kind of exhaust bubble structure in Perfused isolated heart system
CN111480644A (en) * 2019-01-27 2020-08-04 宋红丽 Normal-temperature mechanical perfusion combined with gene modification for repairing small animal organ system by stem cells
CN111480644B (en) * 2019-01-27 2024-02-27 宋红丽 Normal temperature mechanical perfusion and gene modification combined stem cell repair small animal organ system
CN110669669A (en) * 2019-11-05 2020-01-10 西安交通大学医学院第一附属医院 A modular three-dimensional perfusion cell culture system
CN112772638A (en) * 2021-02-24 2021-05-11 吉林大学第一医院 Small animal mechanical perfusion liver temperature control device

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