Sacrificing Alginate in Decellularized Extracellular Matrix Scaffolds for Implantable Artificial Livers.

Abstract

This research introduced a strategy to fabricate sub-millimeter-diameter artificial liver tissue by extruding a combination of a liver decellularized extracellular matrix (dECM), alginate, endothelial cells, and hepatocytes. Vascularization remains a critical challenge in liver tissue engineering, as replicating the liver's intricate vascular network is essential for sustaining cellular function and viability. Seven scaffold groups were evaluated, incorporating different cell compositions, scaffold materials, and structural configurations. The hepatocyte and endothelial cell scaffold treated with alginate lyase demonstrated the highest diffusion rate, along with enhanced albumin secretion (2.8 µg/mL) and urea synthesis (220 µg/mL) during the same period by day 10. A dense and interconnected endothelial cell network was observed as early as day 4 in the lyased coculture group. Furthermore, three-week implantation studies in rats showed a stable integration to the host with no adverse effects. This approach offers significant potential for advancing functional liver tissue replacements, combining accelerated diffusion, enhanced albumin secretion, improved urea synthesis, dense vascular network formation, and stable implantation outcomes.