Antithrombotic Revascularization Strategy of Bioengineered Liver Using a Biomimetic Polymer.

Abstract

A bioengineered liver has the potential to save patients with end-stage liver disease, and a three-dimensional decellularized scaffold is a promising approach for practical use. The main challenge in bioengineered liver transplantation is thrombogenicity during blood perfusion. We aimed to apply a novel antithrombotic polymer to revascularize liver scaffolds and evaluate the thrombogenicity and biosafety of the polymer-treated scaffolds. A biomimetic polymer, 2-metacryloyloxyethyl phosphorylcholine (MPC) was prepared for modification of the extracellular matrix in liver scaffolds. The polymer was injected into the rat liver scaffolds' portal vein and could extensively react to the vessel walls. In an <i>ex vivo</i> blood perfusion experiment, we demonstrated significantly less platelet deposition in the polymer-treated scaffolds than nontreated or re-endothelialized scaffolds with human umbilical vein endothelial cells. In the heterotopic transplantation model, liver volume was better maintained in the polymer-treated groups, and platelet deposition was suppressed in these groups. Additionally, the polymer-treated liver scaffolds maintained the metabolic function of the recellularized rat primary hepatocytes during perfusion culture. The MPC polymer treatment efficiently suppressed thrombus formation during blood perfusion in liver scaffolds and maintained the function of recellularized hepatocytes. Revascularizing liver scaffolds using this polymer is a promising approach for bioengineered liver transplantation. Impact Statement Thrombogenicity is one of the most critical challenges in bioengineered liver transplantation using decellularization techniques. We developed a new strategy for antithrombotic revascularization of bioengineered livers with a biomimetic 2-metacryloyloxyethyl phosphorylcholine polymer to the extracellular matrix. The polymer treatment was demonstrated to be safe for recellularized hepatocytes. This novel approach should be a key for clinical application of bioengineered liver transplantation.