RE-LIVER · Bottom-up reconstitution of a biomimetic bioartificial liver

The liver, by way of its central role in both endogenous and exogenous metabolism, is one of the most well-studied organs in the human body.Hepatic tissue and its derivatives have a wide range of in-vivo and in-vitro applications from whole organ or partial lobe transplant, bioartificial ex-vivo devices, treatment of metabolic disorders to toxicology, drug metabolism and tissue regeneration. On the one hand, suitable donor livers for solid organ transplant are in short supply, while chronic liver diseases are on the increase both in Europe and world-wide. On the other hand, in-vitro and ex-vivo technologies for recapitulating liver function still fall short of reliability, consistency and predictivity, precluding many commercial applications. There is a dire need for innovative and reproducible methods for developing functional bioartificial livers or portions of liver which can be easily transplanted or reliably integrated into extracorporeal devices, essential for treating acute liver failure and other metabolic liver disorders. To avoid the risks and complications associated with animal/human matrices, yet furnish a reliable and reproducible 3D microarchitecture capable of maintaining the detoxification and metabolic functions of healthy human liver, our aim is to fabricate a novel hepatic lobuli ECM replica seeded with stable human hepatocytes and endothelial cells using the human liver as a design template through a bottom up approach. These cell-containing bioartificial constructs will be developed and characterized in vitro to assess metabolic function, protein production and angiogenic potential. They will then be implanted in animal models through minimally invasive techniques as a solid organ transplant alternative to recombinant Factor VIII-based therapy for patients with haemophilia A.