3DBioNet: an integrated technological platform for 3D micro-tissues

Lead Research Organisation: University of Liverpool
Department Name: Institute of Integrative Biology

Abstract

Maybe you have already seen cells under a microscope? Plants, animals and humans are made of cells. For approximately a century, scientists have routinely grown cells on flat transparent surfaces (glass or plastic). Growing cells on flat surfaces is very convenient. In fact, it has been so successful that a lot of what we know about cell components such as the nucleus (which contains the genetic information) and mitonchodria (which provides energy) comes from such experiments; this also includes discovery of drugs and tests of their potential toxicity. However, in real living organisms cells are not attached to a flat surface. Instead, they interact with their three dimensional environment which includes other cells as well as factors secreted by cells. Scientists now realize more and more the importance of this difference between growing cells on a flat surface or growing them in 3D: it modifies their shape, how they communicate with each others and how they respond to changes in their environment. Until recently, animal experiments have been the main alternative to cells grown on flat surfaces. Whilst animal experiments remain essential to our understanding of biology and to the discovery of new drugs, they do not perfectly mimic human biology and it is also desirable to reduce their number for ethical reasons.
In the last decade, scientists have started to culture cells in 3D thereby producing micro-tissues, often starting from stem cells. These micro-tissues made of human-derived cells resemble human tissues. But, just like going from 2D printing to 3D printing requires new materials, new software, new ideas and new procedures, going from 2D cell culture to 3D cell culture requires a large number of innovations in the methods, materials and technologies that scientists use to design, perform, analyse and interpret their experiments. The purpose of the 3DbioNet network is to bring together the skills of scientists from many different disciplines within academia and industry needed to identify the stumbling blocks and help building this new way of doing biology.

Technical Summary

Conventional two-dimensional cell models have helped understand physiology and contributed to the discovery of drugs that have improved human health. Nevertheless, they offer a poor representation of human tissue and its pharmacological response to drugs. Moreover, animal models are often not accurate models of human disease either. Increasing awareness of these shortcomings has led to the development of 3D cell culture models of human tissues or micro-tissues. These have enormous potential for helping to elucidate human physiology, mechanisms of diseases and how these may be safely treated. However, exploitation of these opportunities is limited by major challenges. Drug discovery, cell therapy and personalised medicine applications require new technologies that replicate biophysical cell growth conditions, enhance the reproduciblity of micro-tissue handling and provide analytical options that capture the complexity of the cellular structures that can now be generated. This requires sustained interdisciplinary collaborations and innovations in the physical sciences. The 3DBioNet network assembles researchers who together possess the expertise needed to address these challenges including engineers (3D printing, microfluidics), physicists (advanced imaging, biomechanics), chemists (scaffold materials, dyes with high penetration into tissues), mathematicians (modelling the physiological and pharmacological behaviour of 3D complex systems) and biologists, biomedical scientists and relevant industrial stakeholders. Through the organisation of regular workshops, the use of online communication and collaboration tools, the funding of placements for early career researchers and the award of pump priming funds, we will establish a dynamic multidisciplinary network of researchers from academia and industry that will strengthen the position of the UK as a leader in the field of 3D micro-tissues.

Planned Impact

3DBioNet will benefit members of the public as well as a potential large number of industrial partners.

Members of the public will benefit through improved understanding of science. 3DBioNet's focus area touches on topics where there is a lot of curiosity and debate regularly attracting media attention, e.g. on the replacement of animal experiments and the in vitro growing of tissues and organs. Each activity/grant will be accompanied by a lay report published on the network blog. Awardees will also be encouraged to produce short outreach videos about their work; these will be shared using our social media channels and embedded in our website. We will seek opportunities to engage with the media in relation to our projects and publications, and also each time our network's expertise is relevant to current news. We will contact relevant medical charities, e.g. those who would be impacted by the use of patient-derived in vitro tissue models for determining treatment, and invite representatives to our annual meetings. Members of the public will also benefit via the derived health and economic outputs of the research that will be accelerated by 3DBioNet. In the medium to long term, this area of science is likely to deliver progress in the development of innovative therapies (see examples below) and reduction of animal experiments used in the evaluation of the toxicity and efficacy of new drugs.

Companies in the UK and elsewhere will benefit from 3DbioNet. This is clearly demonstrated by the high level of interest that our proposed network has already attracted at the time of submission. These include start-ups, more established SMEs, and large pharmaceutical companies, which are fully or partly involved in 3D cell culture and micro-tissues. They recognize the need and potential benefit of academic collaborations. As shown by the 13 industry letters of support attached to the proposal, areas of academic-industry collaborations could include tumour spheroids to test anticancer drugs (including personalized medicine based on individual-specific organoids), scaffold-based 3D models of other tissues for drug testing (including liver and cardiac toxicity, skin models), advanced analytical studies and mathematical modelling of these systems for improved better in vitro to in vivo inferences, storage, expansion and scale up of the production of micro-tissues, optimization and beta-testing of cell culture protocols, and, development of an analytical quality assurance training programme.

Publications

10 25 50
 
Description MICA: PANC-AID: Engineering a novel dynamic pancreatic cancer organoid model (MICA)
Amount £432,219 (GBP)
Funding ID MR/V028553/1 
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 08/2021 
End 09/2024
 
Description Biogelx discovery kit 
Organisation Biogelx
Country United Kingdom 
Sector Private 
PI Contribution 3DbioNet provided funding for the travel and secondment award.
Collaborator Contribution Biogelx is an SME based in Scotland. Biogelx participated as a technology provider for the awardees of the travel and secondment awards. The technology was ECM technology for 3D tissue culture and it was provided free of charge to the member of 3DbioNet, Manohar Prasad Koduri , PhD student, University of Liverpool and NTHU, Taiwan.
Impact Multidisciplinary team: Manohar Koduri PhD student, University of Liverpool and NTHU, Taiwan, Dr Jude Curran (School of Engineering, University of Liverpool) , Dr James Henstock (Institute of Ageing and Chronic Disease, University of Liverpool), Professor John Hunt (Nottingham Trent University), - Professor Fan-Gang Tseng (Engineering and System science, NTHU, Taiwan).
Start Year 2019
 
Description Biogelx discovery kit 
Organisation Biogelx
Country United Kingdom 
Sector Private 
PI Contribution 3DbioNet provided funding for the travel and secondment award.
Collaborator Contribution Biogelx is an SME based in Scotland. Biogelx participated as a technology provider for the awardees of the travel and secondment awards. The technology was ECM technology for 3D tissue culture and it was provided free of charge to the member of 3DbioNet, Manohar Prasad Koduri , PhD student, University of Liverpool and NTHU, Taiwan.
Impact Multidisciplinary team: Manohar Koduri PhD student, University of Liverpool and NTHU, Taiwan, Dr Jude Curran (School of Engineering, University of Liverpool) , Dr James Henstock (Institute of Ageing and Chronic Disease, University of Liverpool), Professor John Hunt (Nottingham Trent University), - Professor Fan-Gang Tseng (Engineering and System science, NTHU, Taiwan).
Start Year 2019
 
Description Collaboration: University College London, Manchester BIOGEL, and Royal Surrey County Hospital 
Organisation University College London
Country United Kingdom 
Sector Academic/University 
PI Contribution This collaboration is to undertake research activities gaining from multidisciplinary expertise from Academic, Industry and clinical fields.
Collaborator Contribution UCL (Academic): contributed to the main design of the research project. Manchester BIOGEL: contributed reagents and industry expertise to grow 3D tissues. Royal Surrey County Hospital: contributed to clinical aspects of the study for eg access to patient derived samples.
Impact This collaboration is to undertake research activities gaining from multidisciplinary expertise from Academic, Industry and clinical fields.
Start Year 2019
 
Description Kirkstall Ltd 
Organisation Kirkstall Ltd
Country United Kingdom 
Sector Private 
PI Contribution 3DbioNet provided funding for the travel and secondment award.
Collaborator Contribution Kirkstall Ltd. provided a free starter kit to the award winner of the funding call. Dr Ke Ning, Sheffield Institute for Translational Neuroscience at Sheffield University won the cash award in addition to the Quasi Vivo millifluidic system from Kisktall. Kirkstall have continued to extend the collaboration with 3Dbionet by offering free entry to the early career researcher members of the 3DbioNet to their annual conference Advances in Cell and Tissue Culture.
Impact 1. Training of the award winner on advanced methods of culturing 3D tissue models (mid brain organoids) at world leading laboratory at Johns Hopkins Centre, USA. 2. Application of new technology to projects. 3. Presentation of research outcome in international conference.
Start Year 2019
 
Description Manchester BioGel 
Organisation Manchester BIOGEL
Country United Kingdom 
Sector Private 
PI Contribution Facilitating interactions between the 3DbioNet community and Manchester BioGel.
Collaborator Contribution Sponsorship of two workshops and in kind contribution to a research project co funded by the network..
Impact Dr Adedamola Olayanju became an employee of Manchester Biogel.
Start Year 2019
 
Description Promega 
Organisation Promega Corporation
Country Global 
Sector Private 
PI Contribution The collaboration was aimed to deliver technical training on 3D biology relevant issues and research methodologies. 3DbioNet set up the technical platform to enable the virtual discussions between Promega, a supplier of biological assays and the early career researchers of the network. The network was also successful in obtaining 50% discount offers on a large set of relevant assay kits.
Collaborator Contribution Promega delivered webinars on the following topics: 1. Measuring metabolism in 3D cell culture models. 2. How to validate cell-based assays in 3D cell culture models. Promega also offered 50% discount on many assay kits for 3D cell cultures.
Impact Promega delivered webinars on the following topics: 1. Measuring metabolism in 3D cell culture models. The learning outcomes were: Gaining understanding on the importance of investigating metabolism in 3D cell cultures, factors to consider when choosing a metabolism assay for 3D cell cultures, and ways to maximise data per sample. 2. How to validate cell-based assays in 3D cell culture models. The learning outcomes were: Gaining understanding on factors to consider when choosing a biological assay for 3D cell cultures, and ways to maximise data output per experiment. Promega also offered 50% discount on many assay kits for 3D cell cultures.
Start Year 2021
 
Description Expert opinion Interview for 3DMedNet 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact 3DMedNet published an interview of one of the awardees of 3DbioNet and their expert opinion (2020) on emerging bioprinting technologies and cutting edge research in my lab (http://www.3dmednet.com/users/14012-3dmednet/posts/56765-3d-bioprinting-in-healthcare-opportunities-and-challenges). 3DMedNet is prominent network in 3D printing in medicine, reputed for their publications and journal - 3D Printing in medicine.
Year(s) Of Engagement Activity 2020
URL http://www.3dmednet.com/users/14012-3dmednet/posts/56765-3d-bioprinting-in-healthcare-opportunities-...
 
Description interview for Institute of Mechanical Engineers 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact Awardee of 3DbioNet: Institute of Mechanical Engineers published the interview with the expert opinion on "How printed human organs will speed up future drug development" https://www.imeche.org/news/news-article/how-printed-human-organs-will-speed-up-future-drug-development. Institute of Mechanical Engineers is highly reputed professional body with over 115,000 members in 140 countries.
Year(s) Of Engagement Activity 2021