Biogelx develops and produces materials that mimic the internal environment of the body. These new materials support the growth of cells outside the body in a laboratory environment under more realistic conditions than traditional methods where cells are grown on plastic or glass. Using the Biogelx material allows researchers to study the cells response to test substances such as drugs or toxic agents under conditions that are more similar to the natural environment of the body which in certain circumstances can be used as a replacement to animal testing. The Biogelx team is largely made up of scientists with a background in chemistry who specialize in the development of new materials. To improve their product and expand the services they offer to clients Biogelx need a laboratory facility suitable for growing cells. To set-up a laboratory to grow cells they require the knowledge of a scientist with a biology background who has expertise in this area. This will ensure tests carried out on cells grown on the Biogelx material in the new laboratory facility will meet the appropriate standards and generate reliable results. The secondee, Dr Fiona Murphy, has over 10 years' experience working as a biologist and carrying out both animal testing and experiments on cells grown in laboratory conditions. She is passionate about developing new approaches to conducting research which will reduce the numbers of animals used in biomedical testing while still providing reliable results. The secondment with Biogelx provides Dr Murphy the opportunity to use her experience working as a biologist in a University laboratory to guide the establishment of the biology facility at Biogelx, giving her an insight into working in a commercial laboratory environment. In a series of test-runs of the new facility Dr Murphy will grow cells using the Biogelx platform to ensure the facility is operational up to the appropriate standards. These test experiments will also produce some preliminary results important for Dr Murphy's own research goals. The partnership between Biogelx and Dr Murphy from Heriot-Watt University will help the company to expand and grow and also increase the future career mobility of Dr Murphy through experience gained working in a commercial lab environment.

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

Peripheral nerve injury is debilitating, causing loss of sensation and muscle control, chronic pain and permanent disability. In addition to the serious impact on patients and their families, nerve injuries impact society economically through reduced productivity (nerve injuries predominantly affect young people) as well as the cost of healthcare and rehabilitation. Transected peripheral nerves have the potential to regenerate following surgical repair, but there are serious limitations for injury sites >3cm, because regeneration requires a supportive microenvironment. The current best option is a nerve autograft harvested from another part of the patient's body, but donor site morbidity, limited availability and poor outcome mean there is a clear clinical need to develop effective alternatives. Advances in tissue engineering together with stem cell technologies provide promising routes for engineering living artificial nerve replacement tissues, but progress is limited due in part to a lack of consensus on how to arrange materials and cells in space to maximize nerve regeneration. This is compounded by a reliance on experimental testing, which precludes elaborate investigations due to time and cost limitations. NerveDesign will address this log-jam, by combining mathematical modelling with state-of-the-art in vitro and in vivo experimentation for the first time, to bring about a paradigm shift in the approach used for neural repair. NerveDesign will focus on the chemical and physical stimuli that promote growth of blood vessels and regenerating nerves through a damaged nerve site. Mathematical models will be developed that incorporate the key mechanisms at play - these mechanisms will be quantified through carefully designed experiments that test them in the laboratory. Computer simulations with then be used to test different potential peripheral nerve repair construct designs, and the leading contenders will be fabricated and then tested. This multidisciplinary approach to nerve repair is entirely novel, and delineates an ambitious approach with significant potential for human health impact. To facilitate the uptake of the approach by clinicians, NerveDesign will create and test a user-friendly software tool that enables end users to set construct design parameters according to individual repair requirements. All computational models will be formulated in Systems Biology Mark-Up Language, and published on our websites (alongside an example experimental dataset) to encourage their uptake in a range of nerve tissue engineering applications. Finally, NerveDesign will work with its clinical and commercial Project Partners to directly engage patient groups, and pave the way for translation and commercialisation of the new repair constructs designs.

Bone graft is regularly used in surgery (plastics, maxillofacial surgery and orthopaedics); bone is actually the second most grafted tissue after blood. Ideally the surgeon wishes to take bone from one area (donor site) to another area (recipient site) to support the operation they are performing. However, a patient's own donor bone is in short supply and its removal can lead to complications in the donor site. This means the surgeon will often recourse to allograft - decellularised (and thus biologically inferior) - bone from other people. A third, and growing, option is synthetic graft. Synthetic graft can be made from biologically active materials, but is not viable and thus not yet as good as living bone. Our bioreactor, that supplies nanoscale 'kicks' to cells in culture can be used to convert mesenchymal stem cells (the stem cells of the bone, simple to isolate from a patient's iliac crest or fat tissue) to bone forming osteoblasts. It can achieve this with cells seeded into 3D environments such as gels or potentially synthetic graft materials. This thus allows us to envisage supply of living bone graft derived from a patient's own cells. The ability to supply such materials would provide a new gold standard for bone grafting. In this project we will thus develop our bioreactor into a flexible platform for study of bone regeneration (which will also be of significant interest to many academic labs in the field) and provision of bone graft. Further to this vision of tissue engineered bone supply, there is also a big need in Pharma for relevant bone models to reduce use of both standard lab models that are very dissimilar to the in-body environment and animal testing which has large cost and ethical consideration. Our ability to produce 3D bone in the lab simply, reproducibly, at low cost and without need for chemical control of cell phenotype (we will just use the nanokicks) will provide an excellent model for testing of drugs for e.g. osteoporosis, osteogenesis imperfecta and other bone conditions. In this project, we will use our technique to study 3D bone formation in the lab and look at what metabolites, the basic building blocks of life, the cell use as they form bone. We will then identify bioactive metabolites and validate them in our bone mimics. Finally, we will test to see feasibility of applying nanokicks to humans to help treat e.g. spinal injury, slow bone repair and osteoporosis etc. We will move from mechanical nanokicks to acoustic nanokicks to achieve this.

Biofabrication techniques are used to process natural and synthetic biomaterials, for example including cells, proteins and drugs, in order to create living, tissue engineered structures. These structures are being used to research the development of new drugs and cell-based therapies for a wide range of medical conditions. This research proposal focuses on a new 3D printing technique called Reactive Jet Impingement (ReJI) which can be used for biofabrication. The ReJI technique has some advantages over existing techniques in terms of the number of cells it can deposit within a certain volume, and in terms of the range of the materials and shapes which it can print on. The research programme will focus on three things: (i) Improving the technology, by developing a computational model of the process to support and inform experimental studies, and through scaling up the technology in terms of print capability. (ii) Extending the range of materials which can be processed using the technology. (iii) Applying the technology to the development of clinically relevant tissue models for two selected application areas in drug testing for liver cancer and cardiac tissue engineering.