Abstract
Severe liver disease is one of the most common causes of death globally. Currently, whole organ transplantation is the only therapeutic method for end-stage liver disease treatment, however, the need for donor organs far outweighs demand. Recently liver tissue engineering is starting to show promise for alleviating part of this problem. Electrospinning is a well-known method to fabricate a nanofibre scaffold which mimics the natural extracellular matrix that can support cell growth. This study aims to investigate liver cell responses to topographical features on electrospun fibres. Scaffolds with large surface depression (2 μm) (LSD), small surface depression (0.37 μm) (SSD), and no surface depression (NSD) were fabricated by using a solvent–nonsolvent system. A liver cell line (HepG2) was seeded onto the scaffolds for up to 14 days. The SSD group exhibited higher levels of cell viability and DNA content compared to the other groups. Additionally, the scaffolds promoted gene expression of albumin, with all cases having similar levels, while the cell growth rate was altered. Furthermore, the scaffold with depressions showed 0.8 MPa higher ultimate tensile strength compared to the other groups. These results suggest that small depressions might be preferred by HepG2 cells over smooth and large depression fibres and highlight the potential for tailoring liver cell responses.
Highlights
2 million people per year die worldwide due to liver disease.[1]
The nanoscale surface depressions were fabricated using systems consisting of solvent (chloroform (CFM, CHCl3, Z99%) and methanol (MeOH, CH3OH, Z99%)) and non-solvent (dimethylsulfoxide (DMSO)) at a ratio of 9 : 1 (Table 1)
HepG2 cells were cultured (371, 5% CO2) in T75 flasks with an Eagle’s minimum essential media (MEM) supplemented with 1% L-glutamine, 1% antibiotic–antimycotic, 10% foetal bovine serum and grown to 80% confluence
Summary
2 million people per year die worldwide due to liver disease.[1]. Over 600 000 people in the UK have cirrhosis and since the 1970s the number of deaths due to liver disease has increased by 400%.2 A report published by the Lancet Commission on liver disease in the UK in 2018 indicated that in the future it could overtake heart disease as the biggest cause of death.[3]. A report published by the Lancet Commission on liver disease in the UK in 2018 indicated that in the future it could overtake heart disease as the biggest cause of death.[3] the only effective way to treat liver disease still remains whole liver transplantation, while donor liver demands far outweigh this supply.[2]. Liver tissue engineering is modern biotechnology that is based on combining hepatocyte transplantation with a biomaterial which can mimic a liver tissue environment.[4] This approach can allow cells to survive long-term and maintain a functional phenotype in vitro, which eventually may permit the restoration or replacement of liver functions in the clinical sector.[5,6,7,8] Current research in the field is examining the potential of decellularized whole organ extracellular matrix as one potential avenue to deal with organ shortage. The whole human liver can be decellularized and repopulated with stem cells, which has been shown to exhibit good viability with some function.[9,10] decellularization requires large human or animal resources, which are known to have a wide batch to batch variation.[11]
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