Developing polymeric coatings for mammalian cells offers the opportunity to tune the chemical and physical environment at the cell surface. This emerging technology has the potential to enable significant advances in the field of cell-based therapies and push forward their clinical application in regenerative medicine. One of the most established methodologies to achieve a polymeric coating around cells relies on the use of materials with an overall positive charge that can interact with the anionic cell surface. However, this approach has been proved to be inadequate for the coating of single cells, as positively charged polymers can disrupt the cell membrane and consequently induce cell death. Similarly, the susceptibility of mammalian cells to mechanical and chemical stress has also limited the covalent conjugation of polymer chains through functionalities already present at the cell surface, hence restricting the chemistry available to achieve a homogeneous and long-lasting cell coating. Nevertheless, recent advances have demonstrated that bio-orthogonal click strategies can be used to introduce exogenous functional groups at the cell surface that can be exploited for polymer conjugation. While these strategies have undoubtedly advanced the field of cell engineering, achieving a homogeneous polymer coating with tuneable properties that is able to control cell behaviour remains an unmet challenge. Importantly, investigating how polymer composition and density of conjugation can be exploited to modulate cell behaviour is essential to fully realise the potential of cell coating strategies in the field of tissue engineering and beyond. This is exactly what this project intends to achieve. By developing robust methodologies for single cell coating, we aim to provide a platform to control cell adhesion with the extracellular matrix and surrounding tissue. This is particularly relevant in tissue regeneration, where cells with regenerative potential (tissue-specific or staminal cells) are injected directly into the target tissue and vasculature to promote tissue growth. Often, cell attachment to the existing tissue is low, mainly as a result of inefficient adhesion of transplanted cells to the surrounding environment, which in turn leads to their programmed death and clearance by the circulatory system. In this project, we will use human liver cells as a model system that will allow us to develop the chemistry and deliver fundamental understanding on the polymer structure, molecular weight, and density of conjugation that are needed to achieve a homogeneous cell coating. This cell type has shown great promise for the development of targeted cell-based therapies for liver regeneration. Using liver as a model, our goal is to develop a versatile coating platform that can be applied to a wide range of cells, advancing the field of cell-based therapies for tissue regeneration. The project represents a priority area for the UK and aligns strongly with the EPSRC's prosperity outcomes (Healthy Nation) and the Healthcare Technologies grand challenges. It also tallies with the United Nations (UN) Sustainable Development Goals, specifically Goal 3: 'Ensure healthy lives and promote well-being for all at all ages.'

The lifETIME CDT will focus on the development of non-animal technologies (NATs) for use in drug development, toxicology and regenerative medicine. The industrial life sciences sector accounts for 22% of all business R&D spend and generates £64B turnover within the UK with growth expected at 10% pa over the next decade. Analysis from multiple sources [1,2] have highlighted the limitations imposed on the sector by skills shortages, particularly in the engineering and physical sciences area. Our success in attracting pay-in partners to invest in training of the skills to deliver next-generation drug development, toxicology and regenerative medicine (advanced therapeutic medicine product, ATMP) solutions in the form of NATs demonstrates UK need in this growth area. The CDT is timely as it is not just the science that needs to be developed, but the whole NAT ecosystem - science, manufacture, regulation, policy and communication. Thus, the CDT model of producing a connected community of skilled field leaders is required to facilitate UK economic growth in the sector. Our stakeholder partners and industry club have agreed to help us deliver the training needed to achieve our goals. Their willingness, again, demonstrates the need for our graduates in the sector. This CDT's training will address all aspects of priority area 7 - 'Engineering for the Bioeconomy'. Specifically, we will: (1) Deliver training that is developed in collaboration with and is relevant to industry. - We align to the needs of the sector by working with our industrial partners from the biomaterials, cell manufacture, contract research organisation and Pharma sectors. (2) Facilitate multidisciplinary engineering and physical sciences training to enable students to exploit the emerging opportunities. - We build in multidisciplinarity through our supervisor pool who have backgrounds ranging from bioengineering, cell engineering, on-chip technology, physics, electronic engineering, -omic technologies, life sciences, clinical sciences, regenerative medicine and manufacturing; the cohort community will share this multidisciplinarity. Each student will have a physical science, a biomedical science and a stakeholder supervisor, again reinforcing multidisciplinarity. (3) Address key challenges associated with medicines manufacturing. - We will address medicines manufacturing challenges through stakeholder involvement from Pharma and CROs active in drug screening including Astra Zeneca, Charles River Laboratories, Cyprotex, LGC, Nissan Chemical, Reprocell, Sygnature Discovery and Tianjin. (4) Embed creative approaches to product scale-up and process development. - We will embed these approaches through close working with partners including the Centre for Process Innovation, the Cell and Gene Therapy Catapult and industrial partners delivering NATs to the marketplace e.g. Cytochroma, InSphero and OxSyBio. (5) Ensure students develop an understanding of responsible research and innovation (RRI), data issues, health economics, regulatory issues, and user-engagement strategies. - To ensure students develop an understanding of RRI, data issues, economics, regulatory issues and user-engagement strategies we have developed our professional skills training with the Entrepreneur Business School to deliver economics and entrepreneurship, use of TERRAIN for RRI, links to NC3Rs, SNBTS and MHRA to help with regulation training and involvement of the stakeholder partners as a whole to help with user-engagement. The statistics produced by Pharma, UKRI and industry, along with our stakeholder willingness to engage with the CDT provides ample proof of need in the sector for highly skilled graduates. Our training has been tailored to deliver these graduates and build an inclusive, cohesive community with well-developed science, professional and RRI skills. [1] https://goo.gl/qNMTTD [2] https://goo.gl/J9u9eQ