3D Stem Cell Printing for Animal-Free Drug Development

Lead Research Organisation: Heriot-Watt University
Department Name: Sch of Engineering and Physical Science

Abstract

Printing tissues and mini-organs have recently been achieved by using modified ink-jet printer technology enabling the field
of biofabrication. The novel method of direct printing live cells opens up new paradigm in tissue science and engineering for
drug discovery and therapeutic applications. We have pioneered the world first valve based bioprinter that is capable of
printing human embryonic stem cells without damaging the cells while maintaining their biological functions. This project
aims to develop the first commercial stem cell bioprinter baed on the valve-based printing technology, working in a
consortium led by the global player in robotic control (Renishaw Ltd) and a SME (ClydeBiosciences Ltd) specialised in
developing human heart muscle cells from stem cells for drug testing. We will develop a new type of stem cell printer by
integrating IP protected 3d printing platform from Renishaw with existing valve based cell printing technology. The new
platform will then be validated for producing human heart and liver tissues using human stem cells from leading stem cell
company Roslin Cellab Ltd) and testing their responses to drugs. The new tool will not only allow us to produce high quality
human tissue for potentially more reliable animal free drug testing, but also enable a range of high throughput applications
for pharmaceutical industry, biotechnology companies and stem cell biologists.

Planned Impact

The proposed project will allow us to develop a novel 3d bioprinter to produce 3d tissues from human stem cells for animal
free drug testing, which has huge potential economic and societal impact in UK. In particular, the beneficiaries of this
project will come from the following distinct areas and industry sectors:
1. Impact on Stem Cell Research and Production: The ability to build uniform 3-dimensional tissue has important
applications throughout pharmaceutical industry and stem cell industry. The project will demonstrate the feasibility of
paradigm shifting technology of producing high quality tissues derived from human pluripotent stem cells. This project will
directly benefit pharmaceutical and cosmetic industries by providing high quality tissues that closely relevant to human for
toxicity testing. This could in turn reduce and eventually replace the need for animal testing, offering both economic and
societal benefits. In addition, this will have a significant economic impact on the efficiency and cost of stem cell derived
product and production optimisation. This should lower the overall cost of stem cell manufacturing thereby making
regenerative medicine therapeutics more affordable and accessible to the health service and patients.
2. Impact on Healthcare In the first instance, the cell printing tool has application to all fields of biomedical and clinical
research requiring cell culture, with notable potential in stem cell research, production and process development (biomanufacturing).
Therefore the primary benefit to healthcare will be acceleration of therapy development, particularly in fields of cell-based therapies and regenerative medicine where scale-up can be a block to widespread testing and
adoption. In future developments, the technology can be adapted for use as a medical device, providing bio-artificial
support for patients with end-stage organ disease. Finally, the programme of work could lead to direct in-situ printing tissue
on patients for treating and repairing damaged tissue or organ- benefitting the general public.
.
3. Impact on Biofabrication: Academic researchers working in the field of emerging field of biofabrication (or 3-D bioprinting
for tissue and organ generation) will also benefit from this research through the creation of a next-generation bioprinting
tool. The novel bioprinting method could address some of pressing issues (eg. cell clogging and damage during printing
process) faced by existing bioprinting technologies, advancing an important step further to realise implantable printed
organ. Stem cell biologists moving from 2D culture to 3D tissue culture will need this powerful tool to study 3d cell-cell
interaction, cell-biomaterial interaction and cell differentiation under 3d niche.
4: Knowledge transfer: this project aims to the first stem cell bioprinter which could lead to enormous uptake of the
technology and system by industry. The knowledge transfer is particularly a strong point here, transferring lab research for
industrial product. There is strong potential for the creation of new IPR even within the tight timescale of the proposed
project. Through the close interactions and collaborations with our industrial partner -Renishaw Ltd, Clydebiosciences and
Roslin Cellab Ltd, it will greatly facilitate our research for commercial exploitation.

Publications

10 25 50
 
Description We demonstrated the first bioprinting of iPSC cells (stem cells derived from adult cells) and use the technology to create liver and heart tissues for drug testing without the use of animals. This would be valuable human tissue assay for testing drug toxicity for human drugs more reliably. The new bioprinting technology has also led to new 3D bioprinters now being commercialised by the commercial partners.

We now are extending the approach to create new types of tissues including bones, cartilages and bile ducts.
Exploitation Route 1. Taken up as potential commercial products for new bioprinters.
2. Being used a new research tool by biomedical researchers for creating 3D human tissue models for drug/chemical toxicity testing, stem cell biology, regenerative medicine and modelling human diseases.
3. Use the printing technology to create human tissue/even organs for medical transplantation without the need for organ donation.
Sectors Chemicals,Digital/Communication/Information Technologies (including Software),Education,Electronics,Healthcare,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology

 
Description The findings of this research is being used to create a new 3D bioprinter prototype by Renishaw plc for further commercial applications. In particularly, a follow on research program is being proposed to continue the commercialisation of this platform and the use of two types of in vitro tissue models created by the project-liver and heart. The 3D printing of soft tissue technology has led to a spin out company-Organlike which developed technologies to train next-generation surgeons.
First Year Of Impact 2019
Sector Digital/Communication/Information Technologies (including Software),Education,Electronics,Healthcare,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology
Impact Types Economic

 
Description 3D bioprinting of transplantable bone and cartilage constructs
Amount £194,760 (GBP)
Funding ID EP/P511420/1 
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Public
Country United Kingdom
Start 09/2016 
End 03/2017
 
Description 3D printing multilineage glioma constructs to investigate tumour biology and drug responses
Amount £72,000 (GBP)
Funding ID GN-000344 
Organisation The Brain Tumour Charity 
Sector Charity/Non Profit
Country United Kingdom
Start 09/2016 
End 10/2017
 
Description Donation from Baillie Gifford Ltd
Amount £50,000 (GBP)
Organisation Baillie Gifford 
Sector Private
Country United Kingdom
Start 09/2015 
End 10/2019
 
Description Medical Research Scotland Studentship
Amount £128,918 (GBP)
Organisation Medical Research Scotland 
Sector Charity/Non Profit
Country United Kingdom
Start 09/2015 
End 10/2018
 
Description Small grants
Amount £25,000 (GBP)
Organisation RS Macdonald Charitable Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 02/2015 
End 02/2016
 
Description Renishaw plc 
Organisation Renishaw PLC
Country United Kingdom 
Sector Private 
PI Contribution As partners for this Innovate UK and EPSRC project, Renishaw is actively developing the prototype of the bioprinter for commercial uses based on the research outcome of the program.
Collaborator Contribution Renishaw has provided a whole team of technical developers, project manager, IP manager and etc to support this collaboration. Further funding is being seeked to continue this work beyond the period of this award.
Impact This is a multi-disciplinary collaboration led by Heriot-Watt and Renishaw plc. The partnership is now expanded to multiple organisations including Roslin Cellab, Clydebiosciences Ltd, and Biogelx. A number of groups from universities including Sheffield, UCL, Edinburgh, Glasgow, Newcastle, Swansea are in discussions for further collaboration using the platform we developed.
Start Year 2014
 
Company Name ORGANLIKE LIMITED 
Description Organlike develops 3D printed hyper-real anatomical models for surgical training, surgical rehearsal and planning. Our mission is to support safer and more effective surgery. We aspire to be the global leader producing "hyper-real" organ models and tools for use in surgical simulation, medical training and for the medical device industry. Our hyper-real, high volume, generic surgical training models are produced using our unique materials and traditional manufacturing. 
Year Established 2017 
Impact The company has launched the first home based vascular surgical training programme in the UK, in collaboration with Royal College of Surgeons of Edinburgh. The innovation has been recognised by a top award from British Vascular Society, and more recently by the Global Surgical Training Challenge Discovery Award. Supported by an Innovate UK grant, the Organlike technology has now been applied to train next-generation vascular surgeons in the UK and helping to train paediatric cardiac surgeons in developing countries.
Website http://www.organlike.com
 
Description Exhibition at illumiNations 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Schools
Results and Impact 3D Bioprinting and 3D Scanning technologies were exhibition at the illumiNations: Scottish Closing Ceremony for the International Year of Light 2015. School students and the general public were able to be scanned and to watch demonstations of a 3D Bioprinter working.
Year(s) Of Engagement Activity 2015
 
Description Exhibition in 3D printing show and featured by BBC Click 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact The postdoctoral research Dr. Faulkner-Jones represented the research group to showcase new Bioprinters at the 3Dprintshow 2015 in London, UK. He also gave an invited talk at the 3Dprintshow as part of the medical symposium and got interviewed by BBC click.
Year(s) Of Engagement Activity 2015
URL http://www.bbc.co.uk/programmes/n3csy4hc
 
Description Exhibition in London Science Museum 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Dr Will Shu and his Bioengineering team have demonstrated their 3D stem cell printer at the Science Museum in London, as part of the Museum's Lates programme - a free night for adults that takes place on the last Wednesday of the month. Lates have a different theme each month, spanning issues as far apart as sex, alcohol and climate change.
Year(s) Of Engagement Activity 2015
URL http://www.hw.ac.uk/news/heriot-watt-team-printing-future-london-21845.htm
 
Description International Conference on Biofabrication 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact We delivered talks at the international conference on Biofabrication, Ultrech as planned by the proposal. Over 350 participants attended the leading international conference for the field. Our talk was well received by the audience with interesting discussions.
Year(s) Of Engagement Activity 2015
 
Description Invited Keynote speech at International Conference of Biofabrication 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact This is the leading conference in the area of biofabrication and bioprinting held by the leading regenerative medicine centre at US (Wake Forest Institute of Regenerative Medicine). The invited keynote speech has attracted around 200 participants for the talk and sparked many interesting questions related to the use of sustainable stem cell sources for tissue engineering and 3D biorprinting.
Year(s) Of Engagement Activity 2016
 
Description Publication featured by BBC News 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Media (as a channel to the public)
Results and Impact Our research in reporting the first bioprinting of iPSC stem cells has been published in a featured article at Biofabrication journal. BBC news scotland featured our research entitled: Heriot-Watt researchers print 3D human cells. This is also featured by other media and NC3Rs' news: https://www.nc3rs.org.uk/news/nats-funded-project-claims-breakthrough-bioprinting-cells
Year(s) Of Engagement Activity 2015
URL http://www.bbc.co.uk/news/uk-scotland-edinburgh-east-fife-34586972
 
Description Publication featured by Nature 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact The publication supported by the EPSRC award has led to a research highlight article from Nature, featuring our research and collaboration on the work of 3D bioprinting of DNA based hydrogel for printing organs in the future.
Year(s) Of Engagement Activity 2015
URL http://www.nature.com/nature/journal/v518/n7540/full/518458c.html
 
Description The 3D stem cell bioprinter is acquired by National Museum of Scotland for their collection and exhibition. 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Our 3D stem cell bioprinter is formally acquired by the National Museum of Scotland (NMS). The bioprinter was delivered to the NMS on 14th of March, 2017 and will be exhibited alongside with other scientific objects including Dolly the sheep, in the new science and technology galleries.
Year(s) Of Engagement Activity 2017
 
Description Visit by First Minister of Scotland Nicola Sturgeon 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Policymakers/politicians
Results and Impact The First Minister Nicola Sturgeon and the deputy first minister John Swinney visited Heriot-Watt University to see the cutting edge research and our latest 3D bioprinters. The visit was widely reported in news and social media.

As put in Scottish Government's website: The FM and DFM met Dr Will Shu and his team, inventors of a 3D bio printer, who are a step closer to being able to print organs for transplant or to replace animal testing. Earlier in the month the First Minister set out how a focus on innovation could be a key way to further boost Scotland's economy.
Year(s) Of Engagement Activity 2015
URL https://firstminister.gov.scot/innovation-at-heriot-watt/
 
Description Visit of Chinese Consul General in Scotland 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Policymakers/politicians
Results and Impact Mr Pan Xinchun, the Chinese Consul General in Scotland and his wife Mme Yu Zhili visited Heriot-Watt University to see the ground breaking research being done in 3D cell printing.
Year(s) Of Engagement Activity 2015