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

• Published in: Journal of Zhejiang University. B. Science Vol. 25; no. 6; pp. 499 - 512
• Main Authors: Liu, Hongyi, Zhou, Yuanyuan, Guo, Peng, Zheng, Xiongwei, Chen, Weibin, Zhang, Shichao, Fu, Yu, Zhou, Xu, Wan, Zheng, Zhao, Bin, Zhao, Yilin
• Format: Journal Article
• Language: English
• Published: Hangzhou Zhejiang University Press 01.06.2024; Springer Nature B.V; Xiamen Key Laboratory of Cellular Intervention and Interventional Medical Materials,Xiamen 361004,China; School of Medicine,Xiamen University,Xiamen 361102,China; Fujian Provincial Key Laboratory of Chronic Liver Disease and Hepatocellular Carcinoma(Zhongshan Hospital Affiliated to Xiamen University),Xiamen 361004,China; Department of Oncology and Vascular Interventional Radiology,Zhongshan Hospital Affiliated to Xiamen University,School of Medicine,Xiamen University,Xiamen 361004,China; School of Medicine,Xiamen University,Xiamen 361102,China%Department of Oncology and Vascular Interventional Radiology,Zhongshan Hospital Affiliated to Xiamen University,School of Medicine,Xiamen University,Xiamen 361004,China%School of Medicine,Xiamen University,Xiamen 361102,China%Xiamen Health and Medical Big Data Center,Xiamen 361008,China%Department of Oncology and Vascular Interventional Radiology,Zhongshan Hospital Affiliated to Xiamen University,School of Medicine,Xiamen University,Xiamen 361004,China
• Subjects: Animals; Bilayers; Biomedical and Life Sciences; Biomedicine; Biomimetics; Bionics; Blood flow; Blood Vessel Prosthesis; Blood vessels; Collagen; Crosslinking; Dialysis; Extracellular matrix; Extracellular Matrix - metabolism; Fibers; Fibrosis; Fistula; Fistulae; Hemodialysis; Hepatic Stellate Cells; Hepatitis; Hepatitis B; Hepatitis B virus - genetics; Hepatocytes; Humans; Mechanical properties; Mechanical stimuli; Modulus of elasticity; Polycaprolactone; Polyesters - chemistry; Polyurethane; Polyurethane resins; Polyurethanes; Rabbits; Renal Dialysis; Renal failure; Research Article; Scaffolds; Secretion; Stellate cells; Stenosis; Stimulation; Tensile strength; Thromboembolism; Thrombosis; Tissue Engineering - methods; Tissue Scaffolds; Trans-Activators; Transfection; Viral Regulatory and Accessory Proteins; Mechanical force; 乙型肝炎病毒X基因; 肝星状细胞; gene; 机械力; Extracellular matrix (ECM); 复合双层仿生血管; 细胞外基质; ); Hepatic stellate cells (HSCs); Hepatitis B viral X; Composite bilayer bionic blood vessel; Hepatitis B viral X (HBX) gene; Hepatitis B viral X(HBX)gene; Hepatic stellate cells(HSCs); Extracellular matrix(ECM)
• ISSN: 1673-1581; 1862-1783; 1862-1783
• DOI: 10.1631/jzus.B2300479

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.