The consortium partners are bringing the main state-of the art in the following:
1. Spheroid building blocks and architecture
To translate the spheroid application into the clinic at a later stage, a detailed cGMP roadmap was developed and a company specialized in cGMP-media development was appointed.
CELLS: Hepatocytes/ cholangiocytes issued from adult stem cells with Supporting mesenchymal cells, and endothelial cells in a concentration of~100'000 spheroids/cm3
2. Construct architecture and hydrogel design
The hydrogel formulation has been optimized to respond to different degradation triggers, promoting hydrogel softening and cell proliferation within the 3D hydrogel construct. Embedded spheroids show an increased propensity to sprout and connect together in a 3D cellular network. This outcome will be highlighted in an upcoming publication (planned for the second half of 2023).
Parallel to the crosslinking by mixing mechanism, occurring via Michael type addition, an innovative approach involving the same Michael type addition but this time triggered by UV light was developed. This approach has the advantage that the hydrogel components can be premixed in advance without reacting, allowing a more controlled and user-triggered crosslinking process. Although ultimately not used for the final printing, this approach enables the formation of well-defined 3D hydrogels, printed in a layer-by-layer fashion, and crosslinked with UV light without the use of radicals. This will result in a scientific publication due to the novelty and potential impact.
o Instrumentation
o Spheroid production (KUG plates, MEDICAL plates to upscale the production of spheroids)
o Robotic platform for selective spheroid sorting from multiwell plates using machine learning algorithms
o Bioprinting (RHU): Including a dedicated substrate for printing, incubation, perfusion and transport
o Platform for the unidirectional and continuous perfusion of six 3D printed constructs in parallel in a closed, controlled and sterile environment
ORGANTRANS achievements and results will have expected impacts, for example:
Strengthened position of Europe in translational regenerative medicine
ORGANTRANS presents an opportunity to position Europe to become a pioneer and leader in clinical application of bioengineered livers transplants by (1) demonstrating the technology in relevant environment (TRL6), (2) building complex ecosystem of key stakeholders necessary for successful translation (including end-users), and (3) presenting an actionable plan for fast clinical adoption.
Translational research with short-medium term to clinical trials
The project is intentionally constructed around the integration of various components (3D bioprinter, spheroid sorter, bioreactor, cells, matrix etc.) into the technological platform, which has been tested within the project in vitro as well as in vivo. These preclinical tests validated in vitro functionality of hepatic spheroids or bioengineered liver construct and viability of constructs implanted in in vivo parenchymal environment.
