Engineering of Biodegradable Scaffolds Intended for Liver Tissue Engineering

Abstract

Bioartificial liver-assisted (BAL) devices have been suggested as an alternative strategy for liver transplantation owing to an acute shortage of donor organs. To overcome the fundamental challenge of maintaining hepatic functions in BLAD, a novel strategy was proposed in this study to preserve a mass of highly functional, viable hepatocytes for long-term cultivation in vitro. The strategy involved developing two different types of hybrid scaffolds: an unstructured one comprising random-blended, collagen-grafted PLGA microfibres and crosslinked collagen (PLGA-collagen), versus a structured and defined one comprising collagen strips and a collagen-grafted, three-dimensional scaffold preformed by FDM with gamma-induced collagen polymerisation (PCL-collagen). Both types of hybrid scaffolds exhibited clinically favourable physical and mechanical properties. Furthermore, cell culture experiments revealed that for hepatocytes in these scaffolds which were under perfusion-based coculture with hepatic stellate cells (HSC-T6) or intra-tissue perfusion (ITP) condition, they exhibited enhanced differentiated functions and higher cellular affinity versus their controls. The encouraging results obtained in this study highlighted the optimistic applicability of these scaffolds for liver tissue engineering. The facile approaches rendered herein successfully synchronised natural and synthetic polymers, as well as perfusion-based hepatocyte coculture with HSC-T6 or ITP, thereby paving the way for efficient development of BAL devices and cell-based therapies in the future.