Regenerative devices (scaffolds, biomaterials and interventions) which can repair and regenerate tissues using the patients` own cells, can be translated into successful clinical products and deliver patient benefit at much lower cost and risk and in shorter timescales then other regenerative therapies such as culture expanded cell therapies or molecular (drug) therapies. It is estimated that the global market for regenerative devices will grow to £50bn by 2020 and this offers a real opportunity to grow a £1bn per year industry in the UK in this field. The UK has genuine research strengths in the areas of biomaterials and tissue engineering, musculoskeletal mechanics (prioritised by EPSRC) and regenerative medicine. Regenerative medicine is one of the eight great technologies prioritised across the Research Councils. Research discoveries, new knowledge, outputs and outcomes are often not ready for uptake by industry to take forward through product development to the market and patient benefit. New technologies need to be advanced and de-risked. The clinical needs, potential products and markets need to be defined in order to make them attractive for investment, product development and clinical trials by industry. In the Medical Technologies Innovation and Knowledge Centre (MTIKC) Phase 1, working with industry and clinical partners, we have developed a professional innovation team and a unique innovation and translation process, creating a multidisciplinary research and innovation ecosystem. We have successfully identified research outcomes and new knowledge and created, advanced and translated technology across the innovation valley of death, enabling successful investment (over £100m) by industry and the private sector in new product development. Some products have already progressed to clinical trials and commercialisation and are realising patient benefits. We have established a continuous innovation pipeline of over fifty proofs of concept technology projects. Over the next five years in MTIKC Phase 2, we will address unmet clinical needs and market opportunities in wound repair, cardiovascular repair, musculoskeletal tissue repair, maxillofacial reconstruction, dental reconstruction and general surgery and diversify our research supply chain to over ten other Universities. We will support 150 collaborative projects with industry and initiate forty new industry inspired and academically led proof of concept projects, which are predicted to lead to a further £100m investment by the private sector in subsequent product development. This will enable a sustainable research and product development pipeline to be established in the UK which will support a £1bn / year industry in regenerative devices beyond 2020.

Pressurised gyration processes, which are the focus of this grant application is an emerging technique that utilises centrifugal force and the dynamic fluid flow to jet out advanced functional materials consistently. This technique has shown great potential in overcoming the limitations of the existing techniques to manufacture functional materials and structures that can safely, consistently and cost-effectively be up-scaled. Thus in the past 5 years pressurised gyration, and several sister-processes (infusion gyration, melt pressurised gyration, pressure-coupled infusion gyration) have been developed and applied to prepare functional materials for different applications. The overall motivation of this research is to manufacture a wide variety of "core-sheath" structures, that are not fully exploited commercially in functional applications (e.g. healthcare) simply because of lack of innovative manufacturing. The overall aim of the project is to develop pressurised gyration as a novel means of effective manufacturing of multi-material core-sheath structures. Therefore, a very significant aspect of this project is to develop a pressurised gyration technique based on exploratory experimental evidence, to generate core-sheath structures on a large scale. A newly created exploratory device containing two chambers has been used to manufacture a wide range of polymer nanofibres with different polymers in both aqueous and non-aqueous solutions as core and sheath components at various concentrations, pressures and rotating speeds. In addition antibacterial metallic nanoparticles loaded nanofibres were also produced using this device. The manufacturing of core-sheath structure has been demonstrated by using a high speed camera and microscopy. Thus, the proposed research pays attention on developing a new high yield device for manufacturing layered core-sheath structures based on our existing preliminary device. Also a considerable effort will be devoted to analyse the new process to make quantitative assessment in order to understand the theoretical issues. It will focus on investigating the forming of core-sheath fibres and core-shell capsules from micro-nanoscale. Functionalising those core-sheath structures produced with additions of other, organic, inorganic and particulate materials will be an important feature. The processed core-sheath structures will be characterised with advanced tools to explore their unique physical, chemical and biological properties.

Definition: A rapidly developing area at the interfaces of engineering/physical sciences, life sciences and medicine. Includes:- cell therapies (including stem cells), three dimensional cell/ matrix constructs, bioactive scaffolds, regenerative devices, in vitro tissue models for drug discovery and pre-clinical research.Social and economic needs include:Increased longevity of the ageing population with expectations of an active lifestyle and government requirements for a longer working life.Need to reduce healthcare costs, shorten hospital stays and achieve more rapid rehabilitationAn emergent disruptive industrial sector at the interface between pharmaceutical and medical devicesRequirement for relevant laboratory biological systems for screening and selection of drugs at theearly development stage, coupled with Reduction, Refinement, Replacement of in vivo testing. Translational barriers and industry needs: The tissue engineering/ regenerative medicine industry needs an increase in the number of trained multidisciplinary personnel to translate basic research, deliver new product developments, enhance manufacturing and processing capacity, to develop preclinical test methodologies and to develop standards and work within a dynamic regulatory environment. Evidence from N8 industry workshop on regenerative medicine.Academic needs: A rapidly emerging internationally competitive interdisciplinary area requiring new blood ---------------------

The Centre for Doctoral Training in Tissue Engineering and Regenerative Medicine will provide postgraduate research and training for 75 students, who will be able to research, develop and deliver regenerative therapies and devices, which can repair or replace diseased tissues and restore normal tissue function. By using novel scaffolds in conjunction with the patient`s own (autologous) cells, effective acellular regenerative therapies for tissue repair can be developed at a lower cost, reduced time and reduced risk, compared to alternative and more complex cell therapy approaches. Acellular therapies have the additional advantage as being regulated as a class three medical device, which reduces the cost and time of development and clinical evaluation. Acellular technologies, whether they be synthetic or biological, are of considerable interest to industry as commercial medical products and for NHS Blood and Transplant as enhanced bioprocesses for human transplant tissues. There are an increasing number of small to medium size companies in this emerging sector and in addition larger medical technology companies see opportunities for enhancing their medical product range and address unmet clinical needs through the development of regenerative devices. The UK Life Sciences Industry Strategy and the UK Strategy for Regenerative Medicine have identified this an opportunity to support wealth and health, and the government has recently identified Regenerative Medicine as one of UK`s Great Technologies. In one recent example, we have already demonstrated that this emergent technology be translated successfully into regenerative interventions, through acellular human tissue scaffolds for heart valve repair and chronic wound treatment, and be commercialised as demonstrated by our University spin out Tissue Regenix who have developed acellular scaffold from animal tissue, which has been commercialised as a dCEL scaffold for blood vessel repair. The concept can potentially be applied to the repair of all functional tissues in the body. The government has recognised that innovation and translation of technology across "the innovation valley of death" (Commons Science and Technology Select Committee March 2013), is challenging and needs additional investment in innovation. In addition, we have identified with our partners in industry and Health Service, a gap in high level skills and capability of postgraduates in this area, who have appropriate multidisciplinary training to address the challenges in applied research, innovation, evaluation, manufacturing, and translation of regenerative therapies and devices. This emerging sector needs a new type of multidisciplinary engineer with research and training in applied physical sciences and life sciences, advanced engineering methods and techniques, supported by training in innovation, regulation, health economics and business, and with research experience in the field of regenerative therapies and devices. CDT TERM will create an enhanced multidisciplinary research training environment, by bringing together academics, industry and healthcare professionals in a unique research and innovation eco system, to train and develop the medical and biological engineers for the future, in the emerging field of regenerative therapies and devices. The CDT TERM will be supported by our existing multidisciplinary research and innovation activities and assets, which includes over 150 multidisciplinary postgraduate and postdoctoral researchers, external research funding in excess of £60M and new facilities and laboratories. With our partners in industry and the health service we will train and develop the next generation of medical and biological engineers, who will be at the frontier in the UK in innovation and translation of regenerative therapies and devices, driving economic growth and delivering benefits to health and patients

Anterior Cruciate Ligament injuries are often in the news as they are potentially career ending for footballers and athletes. One of the well-known incidents was seen during 2006 World Cup match between England and Sweden, where Michael Owen ruptured his ACL. This is not just a problem for elite athletes. Approximately 20,000 people in the UK need ACL repair every year and the National Health Service (NHS) performs about 11,000 ACL reconstruction surgeries per year. Reconstructive surgery of the ACL usually involves harvesting replacement ACL graft from the patient's own hamstring tendons. The damaged ACL is removed through arthroscopy (keyhole surgery), then tunnels are drilled in femur (thigh bone) and tibia (shin bone) in the knee joint area. The replacement graft is aligned/positioned through the tunnels, and opposite ends are fixated in the tibial bone tunnel by interference screws. Our clinicians and our medical device partner Xiros have identified an unmet clinical need for new screws and ACL reconstruction devices. Current metallic screws will be eventually rejected by the body as they are bioinert and will undergo fibrous encapsulation, but they can also tear the graft. The aim here is to develop an ideal screw that would be bioactive, to stimulate bonding to bone and regeneration of the connective tissue/ bone interface and biodegradable integrating the graft into the bone. The screw must also be strong, tough and a certain stiffness. Biodegradable polymer/bioactive ceramic composite screws exist, but they often fail and need replacing. This is because the bioactive component is buried in the polymer and the degradation rate of the polymer is uncontrolled and can be catastrophic or cause cysts. Our hybrid screws will overcome those problems, giving strength and a specifically designed biodegradation rate to match the rate of restoration of the bone/connective tissue interface. In some cases, it is not the screw that fails, but the tendon graft, therefore we will also develop a new totally synthetic device that eliminates the need for harvesting from the hamstring and provides more reliable long term performance, while integrating with the host bone.