ORGANTRANS: An EU Project Will Develop a Liver Tissue 3D Printing Platform

Bioengineering our healthcare evolution is what leads researchers to create functional tissues that could one day become the basis to replicate a human organ. With what seems to be a bioprinting revolution underway, we are beginning to witness superior machine development, enhanced bioinks, and a multitude of published research papers leveraging bioprinting as one of the essential tools to strengthen regenerative medicine for the future. One of the latest European Union (EU) Horizon2020 funded projects aims to replace liver transplantation for end-stage liver failure patients through the development of a liver tissue 3D printing platform using bioengineering firm regenHU‘s biofabrication know-how.

The ORGANTRANS (controlled ORGANoids transplantation as enabler for regenerative medicine TRANSlation) project will cover the entire development cycle from cell source and tissue engineering through the trials allowing for early adoption of its results in clinical practice. Moreover, this research aims to create novel technologies that can be applied to other organ systems in regenerative medicine.

Coordinated by Swiss research and development center CSEM, the eight partners and two transplantation centers engaged in the consortium will be using regenHU’s 3D bioprinters to produce organoid-based liver constructs using organoid laden bioinks.

regenHU indicated that ORGANTRANS will tackle the important healthcare challenge of end-stage liver disease (ESLD) and aimed to give patients an alternative to liver donor transplants by capitalizing on advancements in the regenerative medicine field, like using biofabricated liver tissue, to develop an entire value chain from the cell source to tissue engineering, biofabrication, post-processing and testing, and liver transplantation under the “compassionate use exemption” regulation (which provides an important pathway for patients with life-threatening conditions to gain access to unproven human cells and tissue products).

The researchers behind the project expect to eventually supply the regulated tools to engineer a complex liver construct that is safe to undergo clinical translation, allowing for early adoption of its results, for both product and process, in clinical practice.

The Switzerland-based firm claims that the ambitious project and its needs for innovative solutions give regenHU the opportunity to take biofabrication to a whole new level, extending their technologies to the use of organoids in a controlled environment.

Since the 1970s, liver disease has been on the rise, and ESLD, more commonly known as chronic liver failure, affects millions of people around the world. Current, but probably undervalued, worldwide estimations show that 844 million people have this disease, with a mortality rate of 2 million deaths per year. Beyond public awareness, increased diagnosis, and better treatment, ORGANTRANS is seeking more fitting solutions for the disease.

So, how will it work? Under this project’s objectives, patients suffering from ESLD who still have residual healthy liver tissue will be eligible to have adult autologous liver stem cells collected, isolated, self-organized into organoids, assembled by 3D bioprinting, and then matured in a first-of-its-kind combination bioreactor.

“The consortium’s expertise is such that we can combine different environments in the platform that are needed for biomimicry and autonomous self-assembly (organoids) — the two essential elements necessary for bioengineering of a healthy and safe liver construct,” revealed Gilles Weder, Project Coordinator and Applied Biosciences Team Coordinator at CSEM. “Successfully combining these two environments, and then providing the necessary development and testing infrastructure, biomanufacturing and commercializing the outputs and performance validation with an end-user point of view is to the best of our knowledge completely unique.”

ORGANTRANS will capitalize on technology first developed in Europe. Establishing a platform that produces tissue-engineered autologous livers for patients in a personalized, time-sensitive manner is a huge milestone, one that could catapult Europe to the forefront of regenerative medicine. Even though the project’s aim is liver repair, the researchers involved expect that it might have enough scope to be translated in the future to repair or heal other tissues, such as the pancreas.

Wender, who considers that CSEM’s established and broad expertise in the life sciences, drug testing, and regenerative medicine domains makes them an ideal candidate to coordinate the transformation of science into groundbreaking solutions for human health, said that “in this context, we have a strong emphasis on developing Deep Tech, which supports the complete valorization chain from cell source to organ-on-chip systems or engineered tissues.

“Forging strong relations between the members of this consortium, and further developing long-standing relations, such as our partnership with regenHU and Kugelmeiers, only serves to strengthen Swiss small and medium sized enterprises (SME)’s innovative capacities at a European level.”

CSEM will run the project from their research and development headquarters in the Swiss city of Neuchatel, along with the other seven participants, that will combine their advanced know-how to tackle current obstacles for liver regenerative medicine. These include Utrecht University, in the Netherlands; the DWI Leibniz Institute for Interactive Materials in Germany; Belgium’s Vlaams Institute for Biotechnologie (VIB); King’s College London; University of Zurich’s spin-off 3D cell culture company Kugelmeiers; technology scouter Amires, in the Czech Republic; and of course regenHU.

The EU will contribute over 6.3 million Euros to the project that officially began last January and will end in December 2022. Once the researchers develop a liver tissue printing platform, it is expected to be scaled first to Europe and then to the rest of the world.

Project Manager, Martina Nesverova from Amires, emphasized that “throughout all ORGANTRANS’ developmental phases, medical device specifications and regulations will be stringently met, and managed with the support of Kugelmeiers, as well as the end-users – three leading European transplant centers that form the External Advisory Board (including consortium member Kings College London).”

While focusing on customization – one of the pivotal elements of future medicine – ORGANTRANS will collaterally center around patient safety. By replicating the patient’s own stem cells to construct the liver, they are not only creating an alternative to organ donation but also mitigating the chance of organ rejection.

By fostering innovation and research, the platform could become a novel opportunity for biomedical engineering breakthroughs. The potential of this life-changing technology can affect millions of lives, which is why projects like this one are so crucial to the progress of the field. Transforming human cells makes biotechnology an enabler of change, and not just any change, a permanent breakthrough with the capacity to shift the paradigm of healthcare as we know it, revolving around preventing illness instead of curing it.