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

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