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 ORCID:

Hongyi LIU

0000-0002-6005-6511

Yuanyuan ZHOU

0000-0002-0691-954X

Yilin ZHAO

0000-0003-2981-1803

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Journal of Zhejiang University SCIENCE B 2024 Vol.25 No.6 P.499-512

http://doi.org/10.1631/jzus.B2300479


Hemodialysis bilayer bionic blood vessels developed by the mechanical stimulation of hepatitis B viral X (HBX) gene- transfected hepatic stellate cells


Author(s):  Hongyi LIU, Yuanyuan ZHOU, Peng GUO, Xiongwei ZHENG, Weibin CHEN, Shichao ZHANG, Yu FU, Xu ZHOU, Zheng WAN, Bin ZHAO, Yilin ZHAO

Affiliation(s):  Department of Oncology and Vascular Interventional Radiology, Zhongshan Hospital Affiliated to Xiamen University, School of Medicine, Xiamen University, Xiamen 361004, China; more

Corresponding email(s):   15959223830@163.com, zyllbz@gmail.com

Key Words:  Composite bilayer bionic blood vessel, Extracellular matrix (ECM), Hepatic stellate cells (HSCs), Hepatitis B viral X (HBX) gene, Mechanical force


Hongyi LIU, Yuanyuan ZHOU, Peng GUO, Xiongwei ZHENG, Weibin CHEN, Shichao ZHANG, Yu FU, Xu ZHOU, Zheng WAN, Bin ZHAO, Yilin ZHAO. Hemodialysis bilayer bionic blood vessels developed by the mechanical stimulation of hepatitis B viral X (HBX) gene- transfected hepatic stellate cells[J]. Journal of Zhejiang University Science B, 2024, 25(6): 499-512.

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author="Hongyi LIU, Yuanyuan ZHOU, Peng GUO, Xiongwei ZHENG, Weibin CHEN, Shichao ZHANG, Yu FU, Xu ZHOU, Zheng WAN, Bin ZHAO, Yilin ZHAO",
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publisher="Zhejiang University Press & Springer",
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%T Hemodialysis bilayer bionic blood vessels developed by the mechanical stimulation of hepatitis B viral X (HBX) gene- transfected hepatic stellate cells
%A Hongyi LIU
%A Yuanyuan ZHOU
%A Peng GUO
%A Xiongwei ZHENG
%A Weibin CHEN
%A Shichao ZHANG
%A Yu FU
%A Xu ZHOU
%A Zheng WAN
%A Bin ZHAO
%A Yilin ZHAO
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A1 - Hongyi LIU
A1 - Yuanyuan ZHOU
A1 - Peng GUO
A1 - Xiongwei ZHENG
A1 - Weibin CHEN
A1 - Shichao ZHANG
A1 - Yu FU
A1 - Xu ZHOU
A1 - Zheng WAN
A1 - Bin ZHAO
A1 - Yilin ZHAO
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DOI - 10.1631/jzus.B2300479


Abstract: 
Artificial vascular graft (AVG) fistula is widely used for hemodialysis treatment in patients with renal failure. However, it has poor elasticity and compliance, leading to stenosis and thrombosis. The ideal artificial blood vessel for dialysis should replicate the structure and components of a real artery, which is primarily maintained by collagen in the extracellular matrix (ECM) of arterial cells. Studies have revealed that in hepatitis B virus (HBV)-induced liver fibrosis, hepatic stellate cells (HSCs) become hyperactive and produce excessive ECM fibers. Furthermore, mechanical stimulation can encourage ECM secretion and remodeling of a fiber structure. Based on the above factors, we transfected HSCs with the hepatitis B viral X (HBX) gene for simulating the process of HBV infection. Subsequently, these HBX-HSCs were implanted into a polycaprolactone-polyurethane (PCL-PU) bilayer scaffold in which the inner layer is dense and the outer layer consists of pores, which was mechanically stimulated to promote the secretion of collagen nanofiber from the HBX-HSCs and to facilitate crosslinking with the scaffold. We obtained an ECM-PCL-PU composite bionic blood vessel that could act as access for dialysis after decellularization. Then, the vessel scaffold was implanted into a rabbit’s neck arteriovenous fistula model. It exhibited strong tensile strength and smooth blood flow and formed autologous blood vessels in the rabbit’s body. Our study demonstrates the use of human cells to create biomimetic dialysis blood vessels, providing a novel approach for creating clinical vascular access for dialysis.

通过机械力刺激乙型肝炎病毒X基因(HBX)转染的肝星状细胞制备血液透析用双层仿生血管

刘弘毅1,2,周媛媛1,2,郭鹏1,郑雄伟2,陈炜斌1,2,张世超2,付雨1,2,周旭1,万郑1,赵斌3,赵一麟1,2,4,5
1厦门大学附属中山医院肿瘤微创与介入治疗科,中国厦门市,361004
2厦门大学医学院,中国厦门市,361102
3厦门市健康医疗大数据中心,中国厦门市,361008
4福建省慢性肝病肝癌重点实验室(厦门大学附属中山医院),中国厦门市,361004
5厦门市细胞介入及介入医学材料重点实验室,中国厦门市,361004
摘要:人工血管的移植(AVG)造瘘被广泛用于肾衰竭患者的血液透析治疗。然而,目前临床使用的人工血管的弹性和顺应性较差,容易导致狭窄,形成血栓。用于透析的理想人造血管应模拟天然血管的结构和成分,而天然血管主要由血管内细胞分泌的细胞外基质(ECM)中的胶原蛋白维持。研究发现,在乙型肝炎病毒(HBV)诱导的肝纤维化中,肝星状细胞(HSCs)变得异常活跃,并产生过多的 ECM 纤维。此外,机械刺激可促进 ECM分泌并重塑ECM的纤维结构。基于上述因素,我们用乙型肝炎病毒X基因(HBX)转染HSCs细胞,在体外模拟HBV病毒感染的过程。随后,将HBX-HSCs细胞种植入由聚己内酯-聚氨酯(PCL-PU)制备的内层致密、外层多孔的双层支架,通过机械力刺激HBX-HSCs分泌大量的胶原纤维,并促进其与血管支架的多孔结构进行交联。由此,我们获得了一种ECM-PCL-PU复合仿生血管,其在脱细胞后可作为透析用血管。最后,我们将制备得到的血管支架植入兔颈部动静脉瘘模型。该血管支架具有很强的拉伸强度和顺畅的血流,并在兔子体内形成了自体血管。综上,我们的研究展示了利用人体细胞创建仿生透析血管的方法,为创建临床透析血管通路提供了一种新方法。

关键词:复合双层仿生血管;细胞外基质;肝星状细胞;乙型肝炎病毒X基因(HBX);机械力

Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article

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