Automation of 3D cell model assembly by additive printing

This project shall test the feasibility of automating the manufacture of advanced cell-based analysis platforms by additive
printing of platform components. The analytical platforms shall be 3D cell cultures which enhance the function of resident
cells. Additive printing shall deposit biocompatible materials consistently and efficiently in 3D architectures within multiwell
culture plates compatible with medium-throughput analysis. 3D-printed structures designed to mimic tissue architecture
shall be populated with stem cell-derived populations with tissue-specific functionality selected to match the printed
architecture; the feasibility of printing cells directly into these structures shall be studied. For demonstration purposes, the
potential of automated additive printing shall be evaluated using hepatocytes derived from iPS progenitor cells and
deposited in liver-relevant 3D patterns, with model functionality being compared against competing systems and animal
models based on drug-metabolising enzyme levels. The outcome shall be a pre-industrial demonstration of the potential to
apply additive printing in the assembly of 3D cell-based assays used in drug discovery and other industrial processes. This
demonstration will create a springboard for further research and development aimed at automation of advanced cell-based
model assembly to industrial quality standards.

We envisage three main areas of benefit, 1. Economic benefits, 2. Societal benefits and 3. Academic benefit and
advancement of knowledge.
1. Economic Benefits
Two market opportunities will arise from this study.
i) The feasibility of printing cell-based assays will open up a new approach to cost-effective manufacturing of cell-based
systems which can be applied to other cell models and rolled out across this lucrative market sector. Economic benefit and
sector commercial advantage from embracing printing technology will derive both from cost savings during production, and
from the market share securable by making advanced cell models available to a new end-user demographic represented
by smaller organisations conducting lower-volume screening.
ii) An opportunity arises from the new additively-printed cell model developed during the study. An iPS-derived hepatocyte
model offers continuity of cell supply without need for genetic modification of the cell population, and addresses a growing
sub-sector of the cell-based analysis market. The 2010 Visiongain report predicted that "over the coming 10 years, cellbased
assays used for toxicity testing will drive market growth"; "increased demand for more relevant and accurate toxicity
models" was re-emphasised in the report update. Assays based on human hepatocytes are the prime platform for toxicity
testing.
The long-term project outputs shall be a manufacturing expertise capable of assembling cell-based assays in a range of
complexities for a variety of cell types, together with a specific example of an hepatocyte-based assay that has early
exploitation potential.
2. Societal Benefits.
Cell-based assay manufacture by additive printing will make assembly of the complex cell models that bring real preclinical
advances over animal model testing scalable, reproducible and automatable. The down-stream benefit of this enhanced
manufacturing capability will be, firstly, a direct positive impact on animal testing which shall become the more difficult
rather than the easy option in preclinical screening. Secondly, the predictive value of systems based on physiologicallyrelevant
human cells assembled with economy into tissue-reflective architectures will benefit clinical medicine by delivering
better-tested and inherently safer drugs to the clinic.
3. Academic benefits and advancement of knowledge
There will be considerable benefit to academic interests in the UK. This will in two parts. First, the ability to print cells, which
are extremely sensitive to stress and environment conditions, will lay the foundation for an understanding of how to print
individual biological components. Secondly, there will be considerable academic benefit to our understanding of the
interactions between substrate and cell, and how the interface and topology affect the viability of cell cultures.
Commercially sensitive process know-how will be retained within house, but wider more general advances will be shared
amongst the Additive Manufacturing and Regenerative Medicine communities. Full impact will be realised through standard
mechanisms that include academic conference and journal publications and through participation in the EPSRC Centres for
Innovative Manufacturing user days and wider network of academic partners.