Rat liver ECM incorporated into electrospun polycaprolactone scaffolds as a platform for hepatocyte culture
Thomas S. R. Bate, William Shanahan, Joseph P. Casillo, Rhiannon Grant, Stuart J. Forbes, Anthony Callanan
Abstract
Liver disease is expanding across the globe; however, health-care systems still lack approved pharmaceutical treatment strategies to mitigate potential liver failures. Organ transplantation is the only treatment for liver failure and with increasing cases of liver disease, transplant programs increasingly cannot provide timely transplant availability for all patients. The development of pharmaceutical mitigation strategies is clearly necessary and methods to improve drug development processes are considered vital for this purpose. Herein, we present a methodology for incorporating whole organ decellularised rat liver ECM (rLECM) into polycaprolactone (PCL) electrospun scaffolds with the aim of producing biologically relevant liver tissue models. rLECM PCL scaffolds have been produced with 5 w/w% and 10 w/w% rLECM:PCL and were analyzed by SEM imaging, tensile mechanical analyses and FTIR spectroscopy. The hepatocellular carcinoma cell line, HepG2, was cultured upon the scaffolds for 14 days and were analyzed through cell viability assay, DNA quantification, albumin quantification, immunohistochemistry, and RT-qPCR gene expression analysis. Results showed significant increases in proliferative activity of HepG2 on rLECM containing scaffolds alongside maintained key gene expression. This study confirms that rLECM can be utilized to modulate the bioactivity of electrospun PCL scaffolds and has the potential to produce electrospun scaffolds suitable for enhanced hepatocyte cultures and in-vitro liver tissue models.