Poly(ε-Caprolactone) Hollow Fiber Membranes for the Biofabrication of a Vascularized Human Liver Tissue

Abstract

The creation of a liver tissue that recapitulates the micro-architecture and functional complexity of a human organ is still one of the main challenges of liver tissue engineering. Here we report on the development of a 3D vascularized hepatic tissue based on biodegradable hollow fiber (HF) membranes of poly(ε-caprolactone) (PCL) that compartmentalize human hepatocytes on the external surface and between the fibers, and endothelial cells into the fiber lumen. To this purpose, PCL HF membranes were prepared by a dry-jet wet phase inversion spinning technique tailoring the operational parameters in order to obtain fibers with suitable properties. After characterization, the fibers were applied to generate a human vascularized hepatic unit by loading endothelial cells in their inner surface and hepatocytes on the external surface. The unit was connected to a perfusion system, and the morpho-functional behavior was evaluated. The results demonstrated the large integration of endothelial cells with the internal surface of individual PCL fibers forming vascular-like structures, and hepatocytes covered completely the external surface and the space between fibers. The perfused 3D hepatic unit retained its functional activity at high levels up to 18 days. This bottom-up tissue engineering approach represents a rational strategy to create relatively 3D vascularized tissues and organs.