Automated Generation of Dense, Functional and Perfusable Bioprinted Liver Constructs for Transplantation

ongoing

Despite advances in organ transplantation technology, there is still a huge shortage of transplantable organs. Yearly, 25% of patients with end-stage liver disease on the donor waiting list die, emphasizing the need for alternatives to organ donations, such as bioprinting. Bioprinting presents a promising approach for creating organs from scratch, yet, it faces significant hurdles due to technical and biological challenges, combined with lacking standardized procedures and materials. In NEOLIVER, we will develop large, dense, and vascularized fully functional bioprinted constructs suitable for transplantation. We will achieve this by establishing a GMP-conform manufacturing line for standardized production, ensuring unparalleled quality and safety for future patients. More specifically, by using patient-derived organoids and supporting cells including endothelial cells, we will generate millions of multicellular spheroids as building blocks for bioprinting. Through laser induced forward transfer (LIFT) bioprinting techniques we will create a vascularized liver construct via precise spatial deposition of spheroids and vessels at high density. By integrating this technology with extrusion-based bioprinted vessels for blood supply, we will generate the world's first autologous bioprinted liver, ready for transplantation. To show the safety and efficacy, we will transplant the bioprinted liver constructs in immune-deficient pigs. This, combined with a clinical validation plan, upscaling strategy and Health Technology Assessment (including patient acceptance), will prepare the bioprinted liver constructs for first-in-human trials. Thus, NEOLIVER presents a disruptive alternative to donor organs for patients dealing with end-stage liver disease.