regen. ISSUE 5 - SEPTEMBER 2014
THE PATHWAY TO INNOVATION
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CONTENTS
Welcome to regen.
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Joining the regenmed dots – another year of Regener8 connections
Welcome to the fifth issue of regen, the magazine for Regener8 members, keeping you updated on key developments within the Regener8 network and wider sector, providing expert insights and showcasing some of the projects that Regener8 has supported over the last year.
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Regener8’s early career researchers’ network – one year on
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Progress in the fabrications of bioactive cements and pre-set scaffolds for bone tissue regeneration
Focussing on technology, innovation and the future
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The power of partnership
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Five years of successful research translation and commercialisation
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The use of DBM and cellularised DBM in rotator cuff repair
Building the platform for world leading regenerative medicine
To tie in with the theme of our Annual Conference this year, we’ve gathered opinion on the importance of partnerships within the regenerative medicine sector. Kevin Baughan from the Technology Strategy Board discusses building clarity and consensus in the business of regenerative medicine and cell therapies, while Dr Rob Buckle of the UK Regenerative Medicine Platform outlines building the platform for world leading regenerative medicine. Chris Herbert, of the Cell Therapy Catapult, discusses the importance of working with universities to realise the potential for new discoveries, while Peter Zandstra from the Centre for Commercialization of Regenerative Medicine explains how partnering can build the RegenMed industry.
Partnering to build the global regenmed industry
The pathway to innovation for regenerative therapies
Building clarity and consensus in the business of regenerative medicine and cell therapies
In this issue, Regener8’s Mike Raxworthy explains the complex RegenMed environment and how Regener8 is able to look across this landscape and connect players from industry and academia – something which Regener8’s unique position in the sector enables it to achieve. He also looks at some of the key developments this year, particularly the work with strategic partner, the Medical Technologies IKC, in inviting applications for UKbased Proof of Concept projects in priority areas in which the medical technology route to market will be effective for commercialisation. There are a number of case studies featured in this issue of Regen which showcase these excellent projects.
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Urinary tract application for a bladder – derived natural acellular matrix
Small bowel replacement and regeneration
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Islet transplantation for a sustainable cure for type 1 diabetes – all they need is the air that they breathe
Manufacturing bone tissue using resorbable calcium phosphate microspheres loaded with autologous stem cells:
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Working with universities to realise the potential of new discoveries
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Camregen scaffolds for cardiac repair
Regener8 Annual Conference sponsors
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Regener8 membership benefits
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Tissue engineering X systems engineering
One of the most important initiatives that Regener8 has undertaken in the past year is the establishment of an Early Career Researchers’ (ECR) membership stream. On page 22, you can read all about the network, one year on.
CONTACT INFORMATION Regener8, X102 Medical and Biological Engineering, University of Leeds, Leeds, LS2 9JT E: regener8@horizonworks.co.uk Contact details for key members of the Regener8 team can be found on our website at www.regener8.ac.uk
Finally, we’d like to thank our all our sponsors of the Regener8 Annual Conference 2014 for their support.
Regener8 cannot be held responsible for any inaccuracies that may occur, individual products or services advertised, member news or late entries. No part of this publication may be reproduced, scanned or digitally stored without prior written permission from Regener8.
Enjoy reading regen.
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OVERVIEW
JOINING THE REGENMED DOTS – ANOTHER YEAR OF REGENER8 CONNECTIONS By Mike Raxworthy, Operations Director at Regener8
Mike Raxworthy
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At the symposium organised earlier this year1 by Regener8, the Medical Technologies IKC and the KTN, it was observed that “the UK regenerative medicines environment is complex and because Regener8 spans many bodies and organisations it is able to look across this landscape and connect players from industry and academia”. This sums up the motivation behind Regener8 and leads to our distinctive position in working at the interface between industry and academia (and indeed where this joins to clinical practice) to translate work in these sectors into regenerative therapies. The past year has allowed Regener8 to play an important role in strengthening and developing the
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regenerative medicine landscape at a number of points of contact. NATIONAL LANDSCAPE We were pleased to gather around 150 delegates to Regener8’s 2013 conference to consider the challenges and barriers to creating a truly global regenerative medicine (RegenMed) market. Experts reviewed the situation and the prevailing atmosphere in Europe, North America and Asia/Pacific to assess which conditions were most helpful and what remained to be overcome. Not surprisingly, there were few easy answers! What was clear from 2013’s keynote speakers was that, following a longer gestation than many (perhaps
OVERVIEW less informed) observers had predicted, the RegenMed industry is now ready to realise the benefits of good underpinning science, investment in robust manufacturing processes and the emergence of reliable supply and distribution chains. The majority of companies involved in translation to the clinic are small and continue to need to work in consortia with academia and other industry players – at least during part of the bench to bedside journey – to achieve their goals. The important role of the “support industry” – advisors, contract research, testing, manufacturing and clinical trial organisations that have developed a competence in regenerative medicine – was also emphasised by all presenters. Part of Regener8’s role in the UK and beyond is to connect these players and ensure all are aware of the value of collaboration and have the information to benefit from the opportunities that arise. Regener8, together with our strategic partner the Medical Technologies IKC, also led an initiative to invite applications for UK academic-based Proof of Concept (PoC) projects in priority areas in which the medical technology route to market will be effective for commercialisation. A number of excellent projects received funding through this call and, as projects draw to the close of their funding period, will report back to the 2014 conference on progress and on plans and prospects following acquisition of PoC data. Once again, the evidence demonstrates that, as well as a commercial partner, successful projects have needed the input from a number of experts from the support industry. CELL THERAPY CATAPULT 2014 has been a big year for the Cell Therapy Catapult (CTC). As well as moving into newly refurbished facilities at Guy’s Hospital in London and now occupying a state-of-the-art suite of labs and pilot GMP manufacturing space (opened by UK Business Secretary Vince Cable in June), the CTC also has responsibility for bringing the UK Government’s £55m commitment for a large-scale cell therapy manufacturing centre into
operational reality. The Centre, which is expected to open in 2017, is currently at the design and siteselection stage. Regener8 was delighted to agree a Memorandum of Understanding (MoU) with the CTC late in 2013 which will see our organisations collaborating on projects bringing mutual benefits. The MoU agreement with Regener8 allows other centres at the University of Leeds and other partners to bring their expertise on the development and validation of regenerative devices to bear on the cell delivery challenges encountered by CTC as they focus on the development of the UK cell therapy industry. The development of this relationship will be a key priority for Regener8 for the remainder of 2014 and into 2015. PATIENT ACCESS TO REGENERATIVE THERAPIES We have already referred to the Symposium held in York in April 2014. The meeting explored the concept that regenerative therapies are not only truly innovative but are often highly disruptive. This presents particular challenges to achieving market and patient access. Exemplars of new technologies which are transforming care pathways were considered with the National Islet Transplant Programme highlighted as a good case study for the generation of evidence required to justify an NHS-wide infrastructure. Similar approaches may be needed for particular regenerative therapies. The meeting considered the need to stratify patient populations and employ stratified trial designs to generate clinical evidence, to pool data from hospital exemption trials, to reduce the time between regulatory approval and uptake and the need for new reimbursement models for regenerative therapies. A valuable point of contact was established between clinicians, scientists, regulators, industry experts, health economists and funding agencies to review the translational needs of an emergent sector. The output of the Symposium was submitted as a report2 to the UK Regenerative Medicine Expert Group which was set up following the House of Lords Science and Technology Committee enquiry of 2013.
Mark Treherne at Regener8 2013
INTERNATIONAL Regener8 will continue to explore opportunities to build on relationships with international partners such as those visited by Mike Raxworthy in late 20133. Peter Zandstra has written an article in this issue of Regen (page 20) on the scientific priorities being pursued by CCRM. EARLY STAGES Perhaps one of the most important initiatives undertaken by Regener8 over the past year has been the establishment of an Early Career Researchers’ (ECR) membership stream. This group (which already stands at 119 members) allows ECRs to network, and to gain insights into the type of work undertaken by Regener8 member companies through the newly-established industry visits programme. More information on activities will be presented at this year’s conference and on page 22 of this issue of Regen. LOOKING AHEAD It is our hope that Regener8, in partnership with the Medical Technologies IKC, will continue to offer members access to information, collaborative opportunities, training to raise translational awareness and connections to other parts of the RegenMed landscape into 2015 and beyond.
References 1 Achieving Patient Access to Highly Novel and Regenerative Technologies: Enabling Industry to bring Disruptive Innovation to Market, York 9 April 2014 2 http://bit.ly/1mgO59O 3 http://www.regener8.ac.uk/latest-news/art/407/mike-investigates-translation-the-north-american-way.htm
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ANNUAL CONFERENCE
THE PATHWAY TO INNOVATION FOR REGENERATIVE THERAPIES Our 2014 meeting focuses on the Pathway to Innovation for Regenerative Therapies, and brings together world-leading experts from academia and industry to discuss the latest research into pioneering regenerative therapies and technologies, and the progress being made in translating these to the clinic for patient benefit.
The UK is at the forefront of developing regenerative therapies, much of it underpinned by the partnerships that exist between academics and industry. The conference programme this year includes updates from a number of collaborative Proof of Concept research projects that have been funded by Regener8 and the Medical Technologies IKC, and have been carried out by academics working with their industry and clinical partners. These updates will provide an opportunity to learn about the latest innovations in regenerative medicine and their applications in areas as diverse as heart disease, rotator cuff injury, and periodontal disease. Over the last 12 months, Regener8 has established an Early Career Researcher network, and representatives from this group will talk about some of the activities that have taken place – including careers events and company visits. Additionally, this year’s conference again features a poster exhibition, offering a more informal setting in which to learn about a wide variety of research projects - including those
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being carried out by Early Career Researchers. Posters will be available for viewing throughout the day, and delegates will be able to vote for the best poster from an Early Career Researcher. The Regener8 Annual Conference offers a great platform to meet a spectrum of innovators. As one of our keynote speakers this year, Kevin Baughan, Director of Technology and Innovation at the UK’s innovation agency, the Technology Strategy Board, comments: “These are demanding times for the healthcare sector as it seeks both greater efficiency and effectiveness. The opportunities created by scientific breakthroughs in regenerative medicine, from the UK’s world class research base, put us in a unique position to lead the world in this transformative approach to healthcare. “As the UK’s innovation agency, we look forward to continuing our partnership with business and academia in supporting those breakthroughs on their journey through to commercial viability and ultimately, success on the global stage.”
ANNUAL CONFERENCE KEYNOTE SPEAKERS THIS YEAR INCLUDE:
KEVIN BAUGHAN
Director of Technology and Innovation, Technology Strategy Board
ROB BUCKLE
MRC Director of Science Programmes and Director, UK Regenerative Medicine Platform
Kevin is an experienced and innovative telecoms professional who was previously Director of Wireless at Virgin Media Business. He was responsible for developing Virgin Media’s metro wireless propositions, including the rollout of WiFi on the London Underground. Prior to this, Kevin cofounded a start-up carrying out pioneering research into novel networking technologies for the US Air Force Research Labs with colleagues at the University of Birmingham. He holds a BSc from Birmingham University, an MSc in Computer Science from Aston University and an MBA with distinction from Imperial College. He was an Honorary Professor from 1999 to 2008 at Birmingham University, where he advised the University’s communications research team.
WILFRIED DALEMANS
Chief Technical Manager, TiGenix
Before joining TiGenix, Wilfried held management positions in GlaxoSmithKline Biologicals where he was responsible for the worldwide registration of GlaxoSmithKline’s flu franchise. With this firm, he also served as Director of molecular biology and research, responsible for the development of nucleic acid and tuberculosis vaccines, as well as immunology research activities. Prior to joining GlaxoSmithKline, Mr. Dalemans worked at Transgène, France, where he was responsible for the cystic fibrosis research program.
Industry in the 2011 New Year’s Honours list. His career has seen him work for ICI, MedImmune Cambridge and AstraZeneca. He has worked on industrial biotechnological processes including Pruteen, Biopol and competitive biopharmaceutical strategies.
Dr Rob Buckle is the MRC Director of Science Programmes and Director of the UK Regenerative Medicine Platform, a national translational programme sponsored by BBSRC, EPSRC and MRC. Rob has been with MRC since 2000, and has previously been Head of Theme for both Stem Cells and Regenerative Medicine and Neurosciences and Mental Health at the MRC. Prior to that Rob worked for ten years in research, studying gene regulation, cell cycle and early development, both in academia and industry.
JOHN STAGEMAN
Chair of the Biomedical Catalyst Major Awards Committee Dr John Stageman is a lay Governor of the University of Manchester where is also an Honorary Professor of Life Sciences. John has received an OBE for his services to the UK Biotechnology
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Nationally John was Chairman of the HealthTech and Medicines Knowledge Transfer Network for the Technology Strategy Board (TSB), a Council member of the Biotechnology and Biological Sciences Research Council (BBSRC) and is currently Chairman of the Major Awards Committee of the Biomedical Catalyst on behalf of the MRC and TSB. Regionally John was a former non-executive Board member of the NWDA and is Chairman of Bionow, a specialist life-science and biomedical business support organisation for the North of England.
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TECHNOLOGY AND INNOVATION
BUILDING CLARITY AND CONSENSUS IN THE BUSINESS OF REGENERATIVE MEDICINE AND CELL THERAPIES By Kevin Baughan Director of Technology and Innovation at the Technology Strategy Board
There is something powerful and compelling in the potential of regenerative medicine. Using the processes already present within human biology to replicate or regenerate cells, tissues or organs offer a wealth of new possibilities for treating and curing diseases. It is an approach to medicine which feels both highly transformative and yet at the same time reassuringly intuitive. Finding such winning combinations in new technologies is always appealing, as it points not only towards the potential for a true step change in outcomes, but also towards widespread acceptance and a smoother path towards achieving large scale adoption. As the UK’s innovation agency, it is our role to accelerate economic growth by connecting, funding and supporting business-led opportunities created through new technology. We see opportunities which have been created by exciting scientific breakthroughs from our world class UK research base. We see opportunities which result
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from bringing together existing UK capabilities and strengths in order to tackle new problems or to create new ways of addressing existing ones. Society also faces a number of fundamental challenges and as a result we see opportunities in areas such as health, transportation and energy. At the Technology Strategy Board, we are often at our best when all three of these combine in one programme, as they do in the case of regenerative medicine and cell therapies. This is an exciting domain where world leading scientific breakthroughs from our universities combine with our core strengths in high value manufacturing, tissue engineering, biomaterials, cell therapy, gene therapy and chemical biology. Businesses want to know that they can execute on their plans robustly and successfully before they start. I see the role of my team in the Technology Strategy Board as working to progressively build confidence in the areas which are addressed by our portfolio of
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targeted innovation programmes. It’s a journey that will often see us progressing concepts from research into translation and then from translation into commercialisation before they can eventually become business as usual. At the start of the journey, during the research and translation phases, when there are very high levels of uncertainty and multiple competing perspectives, it often falls to the leadership and judgement of key individuals within the sector in order to build momentum, confidence and excitement around the potential of an opportunity. As the journey moves through commercialisation, it will become progressively less dependent on the thought leadership of individuals and instead become increasingly dominated by financial and operational processes. For the last seven years, the Technology Strategy Board has been focused on improving the journey of UK innovators from concept to commercialisation and in the specific case of regenerative medicine and cell therapies, we are proud to have
TECHNOLOGY AND INNOVATION been able to play a part in building the UK’s leadership position. A great example of how we can use our targeted innovation programmes to connect, fund and support ambitious businesses on the journey from concept to commercialisation is the experience of Gregg Sando and Karin Hodgkin at Cell Medica. It started with them submitting two grant applications at the same time, one of which was accepted and the other rejected - a reminder that not every proposal will be considered robust enough to progress from one phase to the next. Indeed, in the absence of clarity and consensus it is very likely that different parties will have different perspectives on the same proposal. Our own competition-based approach, where we focus on designing the race course, rather than on picking the winners, has served us well. In the case of Cell Medica it allowed them through their first successful grant application, to proceed with confidence in developing a new low-cost manufacturing method. They then subsequently won two further grants: one to establish a collaboration agreement with Great Ormond Street Hospital and University College London, and another to then take into clinical trials at GOSH, a cell therapy treatment which would stimulate the body’s own immune system to tackle life-threatening infections following bone marrow transplants. The grants Cell Medica received from the Technology Strategy Board came from programmes covering high value manufacturing as well as from regenerative medicine and cell therapy, highlighting the benefits of allowing each of our targeted innovation areas to draw on expertise from right across our multi-disciplinary team. Cell Medica has now flourished into a global company which has subsequently attracted substantial additional investment in order to focus on a multi-billion pound market. It has been able to develop strengths in commercial manufacturing, regulatory approvals as well as in reimbursement, marketing and distribution. Strengths which have allowed them to build clarity and consensus around the business models they are pursuing. While Cell Medica is a great example of how we can work in
partnership with a single business, the Cell Therapy Catapult is a superb example of how we can work to energise an entire sector. Its vision is centred on establishing the UK as a global leader in the development, delivery and commercialisation of cell therapy. It sees itself as a facility where businesses can start, grow and confidently develop cell therapies which are in turn delivered to patients rapidly, efficiently and effectively. It received a major boost earlier in the year when it was also awarded a further ÂŁ55m in order to establish a large-scale cell therapy manufacturing centre in the UK. Since 2011, the Technology Strategy Board has established seven Catapults and in 2015 we will
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launch two further Catapults; one in precision medicine and one in energy systems. These leading edge innovation centres act as a focal point to bring under one roof the very best domain expertise from academia, business and engineering together with critical assets (both digital and physical) in order to allow an entire sector to work together. These are both exciting and demanding times for the healthcare sector and I look forward to continuing the momentum we have already established. For further information visit: www.innovateuk.org
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CASE STUDY
PROGRESS IN THE FABRICATION OF BIOACTIVE CEMENTS AND PRE-SET SCAFFOLDS FOR BONE TISSUE REGENERATION. By Paul Hatton, School of Clinical Dentistry, University of Sheffield Researchers at the University of Sheffield have made significant progress in the development of a new bone cement and pre-set regenerative scaffold based on the combination of bioactive glass with an acidic polymer.
Individual granule of pre-set ionomeric bone graft substitute
Glass ionomer cement
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For over 20 years, researchers have been seeking a cement composition which does not release aluminium ions; glass-ionomer cements currently used in middle ear surgery contain aluminium ions - often associated with local bone tissue mineralisation and neurotoxicity. Improved understanding of the complex setting chemistry has assisted the design of optimised materials. Our new cement contains no aluminium and is more biocompatible then previous compositions. Further progress includes preparation of both prototype cements and bone graft substitutes or scaffolds, and demonstration of in vitro biocompatibility using cultured L929 cells showing the new material is comparable to the parent bioactive glass composition. The study of tissue response using
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a challenging bone defect model has been initiated. In addition, a patent that describes this new technology has been published (WO2014102538A1). The new biomaterials are very much ready for development as medical devices, and towards this goal the team have received an indepth market analysis report from Christina Doyle of Xeno Medical Ltd, detailing important opportunities. With this goal in mind, discussions with potential commercial manufacturers and end users are now being undertaken. This new technology could have applications in the treatment of a number of ear conditions such as ossicular chain repair and Cochlear implant surgery. Potentially, it could also have wider uses as a bone graft substitute for use in craniofacial, orthopaedic, dental and spinal surgery. This project is highly likely to lead to the deployment of new healthcare technologies for patient benefit. For further information visit: www.sheffield.ac.uk/dentalschool/ research
CASE STUDY
THE USE OF DBM AND CELLULARISED DBM IN ROTATOR CUFF REPAIR By Professor Gordon Blunn, Director Institute of Orthopaedics and Musculo-Skeletal Science, University College London Figure 1
The project funded by the Medical Technologies IKC investigates the use of decellularised and demineralised bone as construct for repairing avulsed rotator cuff tendons and regeneration of the enthesis.
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Current augmentation strategies are aimed at improving the healing process and preventing early failure by trying to recreate a normal healthy enthesis. However, mixed results for surgical outcomes are reported and an inflammatory reaction remains a common complication resulting in the accumulation of dense poorly organised fibrous tissue at the healing enthesis.
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Our work has shown that using demineralised bone at the interface between tendon and bone leads to a faster functional recovery and the formation of an enthesis that has morphology similar to the normal bone tendon junction (Sundar et al. 2009). Further work has shown that demineralised bone can be used to bridge a larger defect between the tendon and the bone, which occurs in chronic tears where the tendon retracts away from the bone surface (Figures 1-4). The work funded by the IKC investigates the use decellularised and demineralised allografts and xenografts, made from cortical bone, which have been augmented with
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minimally manipulated autologous stem cells. The work has shown that in vitro demineralised allografts can induce differentiation of stem cells into chondrocytes and the trans-differentiation of tenocytes into chondrocytes, which produce a collagen type 2 matrix. In vivo tests are being carried out. We have found that incorporating the buffy layer into fibrin glue at the time surgery retains the cells from the buffy layer within the defect adjacent to the demineralised bone. In vitro tests have shown that cells are able to remain alive and proliferate in the fibrin glue over a 96-hour period. In the in vivo model there appears to be no difference between xenograft and autologous demineralised bone. Figure 1: Per-operative photograph showing the resected patellar tendon (arrowed) with suture anchors in the tibial tuberosity. Figure 2: Demineralised bone strip sutured into the remains of the patellar tendon. Figure 3: Photograph of the remodelled tendon at retrieval taken after 12 weeks duration. Figure 4: Histology photograph of the tibial tuberosity with the remodelled tendon insertion and the remodelled demineralised bone. For further information visit: www.medical-technologies.co.uk
References Sundar S, et al. Tendon bone healing can be enhanced by demineralized bone matrix: A functional and histological study. JBMR (A) 2009;88(1):115-22
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UK LANDSCAPE
BUILDING THE PLATFORM FOR WORLD LEADING REGENERATIVE MEDICINE By Rob Buckle Director, UK Regenerative Medicine Platform The UK Regenerative Medicine Platform (UK RMP) is a cornerstone to the strategy for UK Regenerative Medicine and aims to address the technical and scientific challenges associated with translating promising scientific discoveries in this area towards clinical impact, specifically the current regenerative medicine bottlenecks and knowledge gaps. Critically, it provides a focus to align effort and connect more fundamental discovery science to application. Jointly funded by the Biotechnology and Biological Sciences Research Council (BBSRC), Engineering and Physical Sciences Research Council (EPSRC) and Medical Research Council (MRC), the Platform has been delivered in two stages. Stage one was the award of £20m to establish five interdisciplinary research Hubs to provide the critical mass needed to overcome key translational challenges and new tools, protocols and resources that can be utilised by other UK research groups in academia and industry. The key feature of the Hubs is the assembly of interdisciplinary skills
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such as stem cell biology, imaging, immunology, tissue engineering, nano/materials and manufacturing science. Each will focus on tackling a particular challenge related to translation. The five Hubs are: • Cell behaviour, differentiation and manufacturing Hub Director: Professor Peter Andrews, University of Sheffield in collaboration with Cambridge and Loughborough universities, the Babraham Institute and the UK Stem Cell Bank. • Engineering and exploiting the stem cell niche Hub Director: Professor Stuart Forbes, MRC Centre for Regenerative Medicine, University of Edinburgh with multiple research organisations including Cambridge, Imperial College London, Keele, Kings College London, Liverpool, Manchester and Strathclyde. • Safety and efficacy, focussing on imaging technologies Hub Director: Professor Kevin Park,
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MRC Centre for Drug Safety Science, University of Liverpool with Edinburgh and Manchester Universities, and UCL. • Acellular (smart material) approaches for therapeutic delivery Hub Director: Professor Kevin Shakesheff, University of Nottingham, with Imperial College London, Keele, Manchester, Southampton, Birmingham, Sheffield, Swansea and Cambridge universities. • Immunomodulation Hub Director: Professor Fiona Watt, King’s College, with University of Birmingham, Cancer Research UK London Research Institute, Imperial College London, Newcastle and Oxford universities and University College London. The central focus of the Cell behaviour, differentiation and manufacturing Hub is the development and optimisation of manufacturing processes for consistent and scalable production
UK LANDSCAPE of pluripotent stem cells and progenitors to meet the requirements of clinicians, regulatory authorities and industry for safe and costeffective applications. The Niche Hub seeks to understand the biology of what we call the stem cell ‘niche’ – the microenvironment in which cells grow or are placed. By understanding aspects such as growth factors, signalling molecules and molecular targets that can influence how cells grow and differentiate, as well as the differences in the niche between normal and disease states, the innate biology can be harnessed and exploited. The remit of the Safety Hub is to provide a clearer understanding of the potential hazards (and associated risks) of regenerative medicine therapies. For example, what is the fate and consequence(s) of cells administered within the body if they don’t remain in the target tissue or organ? The safety Hub will develop new ways of assessing their risk, so that new medicines based on cell therapy can be developed with full confidence. The Acellular Hub will use a range of materials from natural and synthetic sources to coordinate cells to regenerate tissue. This could mean using drugs to stimulate or mobilise stem cells within a patient’s own body, or might involve using cells themselves as a therapy. The use of transplanted stem cells irrespective of whether they are autologous (self) or allogeneic (non-self) cells can evoke immune responses which can represent a formidable obstacle to success. The Immunomodulation Hub will determine how to harness the immune system for improved outcomes in regenerative medicine. The Hubs will work in synergy to provide world-leading interdisciplinary expertise and the critical mass needed to address key challenges in regenerative medicine. They are designed to evolve over time to incorporate new partners as required, be that academic or industrial, to continue to address existing and emerging issues within the field. In this way they will provide solutions to the relevant problems of regenerative medicine to
ultimately allow scientific advances to be translated to clinical and commercial application. Stage two of the initiative is £6m in awards, in partnership with Arthritis Research UK, supporting cutting-edge research consortia at UK research institutions. People suffering from diseases including osteoarthritis, age-related macular degeneration, liver disease and nonunion bone defects will benefit from these multidisciplinary translational regenerative medicine programmes. They will build upon the stage one investments by integrating with activities of the existing Hubs. The five programmes are: • Professor Charles Archer, Swansea University – Generating durable and resilient repair of cartilage defects using tissue-specific adult stem cells – a systematic, therapeutic approach; • Professor Pete Coffey, University College London – Scalable production of RPE cells from induced pluripotent stem cell under GMP conditions for cellular replacement therapy of the dry form of Age-related macular degeneration (AMD); • Professor Andrew McCaskie, University of Cambridge – Stepwise Translational Pathway for Smart Material Cell Therapy (SMART STEP), which will be focused on osteoarthritis; • Professor Salmeron-Sanchez, University of Glasgow – Synergistic microenvironments for nonunion bone defects, with the aim of increasing natural bone regeneration and healing capacity; • Dr David Hay, The University of Edinburgh – The development of 3-dimensional implantable liver organoids, with the aim of providing alternative renewable solutions to organ transplantation in the treatment of human liver disease. The awards to Archer and McCaskie provide collaborative research components between UK and Dutch partners adding additional expertise to the consortia with the funding of the Dutch component of work met by Reumafonds, the Dutch Arthritis Foundation. Finally, the UKRMP provides essential connectivity to maximise the impact of other strategic investments in
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this field. We are working closely with the UK Cell Therapy Catapult, and the British Heart Foundation – which has established three national centres in cardiovascular regenerative medicine. The Platform also has links to the UK Stem Cell Bank and the MRC/Wellcome Trust Human iPSC Initiative to ensure technological developments play into the provision of high quality cell lines to the research community, while the overall strategic approach has further benefitted from the injection of £20M capital funding in 2013 in alignment with the Platform and these associated developments. The UKRMP will create visibility for translational research in the UK attracting investment and the formation of new partnerships. This will give rise to a world-leading and fully connected national programme able to pull discovery science towards commercial development and clinical delivery of regenerative medicine products that will ultimately benefit patients. For further information visit: www.ukrmp.org.uk
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CLINICAL
ISLET TRANSPLANTATION FOR A SUSTAINABLE CURE FOR TYPE 1 DIABETES – ALL THEY NEED IS THE AIR THAT THEY BREATHE By James Shaw, Professor of Regenerative Medicine for Diabetes, Newcastle University Transplantation of insulin-secreting pancreatic islets from deceased organ donors is established within the NHS as a successful and sustainable cell therapy for long-standing type 1 diabetes complicated by recurrent lifethreatening low glucose reactions (hypoglycaemia).
on a particularly dense network of blood vessels being absolutely dependent on an uninterrupted oxygen supply. Donor death severs the connection to the circulatory network leaving the core of these islands of tissue without oxygen until new blood vessels grow following transplantation.
It is often stated that the limiting factor for cell transplantation for diabetes is insufficient beta-cells justifying the need for novel stem cell-derived sources. There are, however, sufficient organ donors under the age of 60 years to transplant all of the patients on the current UK islet transplant waiting list every year.
In Newcastle we are exploring a range of innovative approaches to limit islet hypoxia during all bioprocessing steps:
In reality there are two major factors preventing provision of this regenerative medicine therapy to the 300,000 people with type 1 diabetes in the UK: 1. Inability to reproducibly deliver sustainable insulin independence from a single minimally invasive transplant procedure. 2. Need for toxic life-long immunosuppression to prevent rejection of the foreign graft and recurrent diabetic autoimmune attack. A single transplant should be more than enough but 50% of transplanted islets are irreversibly damaged through oxygen starvation and lost over the first week before they can re-establish a blood supply from the transplant site in the liver. In the native pancreas, islets rely
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Pancreas persufflation bubbles oxygen through the vasculature following organ retrieval. The goal is to maintain islet viability and metabolic health while the organ is transported to the islet isolation facility. Underpinned by persuasive proof-of-concept data and in collaboration with Dr Klearchos Papas at University of Arizona, we propose a national randomised controlled trial comparing persufflation with standard pancreas preservation in all organs offered for clinical transplantation in the UK. Following isolation, islets are maintained in standard suspension culture and may subsequently require transport to a distant transplant centre. As a cluster of cells which may be up to 0.5 mm in diameter, oxygen limitation within the core often leads to central necrosis, inducing an instant inflammatory response post-transplantation leading to a major loss of functional mass. We are exploring a range of novel bioreactor approaches aimed at maximising islet health and
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oxygenation post-isolation and pretransplantation. Ischaemia persists for many days post-transplantation through the requirement for development of a new host-derived vascular network at the site of transplantation. Working with collaborators in Israel, we are currently exploring ex vivo combination of islets with recipientderived blood cells enriched for endothelial progenitor cells to facilitate revascularisation posttransplantation, minimising hypoxic stress and maximising engrafted transplant mass. Immunobarrier encapsulation of islets promises transplantation without the need for systemic immunosuppressive drugs, thus avoiding the associated risk of severe infections and malignancy. An effective barrier also prevents islet revascularisation and is thus associated with necrotic cell death. In situ oxygenation provides a potential solution. This is currently being pioneered through subcutaneous transplantation of islets within a macro-encapsulation device which is then injected percutaneously with oxygen. Overall it is envisaged that transformative enhancement of clinical transplant outcomes will be achieved in the near future through a range of innovations targeting and attenuating islet hypoxia. For more information visit: www.ncl.ac.uk/ctf/about/ background.htm
NETWORKS
WORKING WITH UNIVERSITIES TO REALISE THE POTENTIAL OF NEW DISCOVERIES By Chris Herbert, Cell Therapy Catapult
The cell therapy industry has various challenges to overcome...Here Chris Herbert, Business Development Executive at Cell Therapy Catapult discusses the importance of collaboration between industry research, academics and TTO’s and the new scheme developed to benefit both the Universities and the cell therapy industry. Bringing together universities and the Cell Therapy Catapult - that’s my remit as part of the business development team. With noncommercial organisations carrying out the majority of late-stage preclinical research and clinical trials in the UK, universities are an important partner for us. And since UK university research is considered world-class, with an estimated £100m in academic funding available per annum, it’s the ideal foundation upon which to build the UK cell therapy industry. It’s a really interesting role enabling me to spend time talking to academics about their latest research, talking to the technology transfer offices and working with
them on maximising the impact of their breakthrough research on the growth of the UK cell therapy industry. As I’ve criss-crossed the UK talking to academia, particularly those in the N8 grouping, I’ve been really struck by the variety and quality of research. Great news for the future of the industry - but how to capture this value? Across my discussions with the technology transfer offices (TTOs), some common themes have emerged that highlight the challenges they face in trying to do so. These include the lack of obvious commercialisation routes, given the early-stage nature of the industry and its risk perception within the investment community, the length of development time for new therapies, budgetary constraints, plus sometimes lack of access to in-depth cell therapy expertise. Further discussions revealed that academics and TTOs were as exercised about these challenges as we were, and that there was appetite for us to work together to tackle them. So we came up with what we believe is a neat and elegant solution. The Cell Therapy Catapult has initiated as a 12-month pilot an Intellectual Property Protection and Access scheme, under which we will work with universities to help them capture the value of novel IP, in a way that still enables them to meet their obligations to stakeholders.
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The aim is to promote early patent filings around what we believe to be valuable IP, guarding against early disclosure and enabling academics to publish freely thereafter, safe in the knowledge that the opportunity to secure an IP position has not been lost. Under the scheme, promising developments where there is potential to secure an IP position undergo review using expertise at the Cell Therapy Catapult. If it looks like there is an opportunity worth pursuing, the Cell Therapy Catapult pays a technology access fee which is used to support initial patent filings, in return for a non-exclusive licence to use the technology internally, and an option to commercialise it later. It’s early days for the scheme and it’s going well so far. The Cell Therapy Catapult has really enjoyed working with both academics and the TTOs to develop a scheme of benefit to both Universities and the UK cell therapy industry - one that will hopefully produce many exciting new projects and therapies. Dr Chris Herbert is part of the Business Development team at the Cell Therapy Catapult, with particular responsibility for engagement with University research groups and technology transfer offices. For more information visit: www.catapult.innovateuk.org/celltherapy
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Products . Research . Consulting
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CASE STUDY
CAMREGEN SCAFFOLDS FOR CARDIAC REPAIR By Professor Serena Best, University of Cambridge
The aim of the CamRegen Scaffolds for Cardiac Repair project is the development of three-dimensional environments to promote regeneration of cardiac tissue. Heart disease is currently the leading cause of death and disability in the world. This burden is predicted to rise in the future due to an ageing population and increasing prevalence of cardiovascular disease. To date there is a critical unmet need for cost-effective treatment of cardiac disease. Improved treatment options for cardiac repair offer the potential for more rapid patient recovery, reduced hospitalisation time and reduced cost to the NHS. It is possible to partially repair diseased myocardium using multiple epicardial injections of functional cardiomyocytes. Despite this up to 90% of these implanted cells die or migrate elsewhere. Additionally cell injections do not provide mechanical support for, or structural integration with, the host tissue. In contrast to these interventions, the use of three-dimensional scaffolds can provide a cell niche and can act as a more effective cardiac repair vehicle.
Figure 1 - SEM of a porous collagen-based scaffold
To date the award provided by Regener8 has allowed development of collagen scaffolds that support superior cellular functions. Therefore these improved scaffolds offer a combination of excellent mechanical and degradation properties whilst simultaneously retaining native-like cell-collagen interactions. The funding provided by the IKC PoC scheme has provided research capacity to allow us to demonstrate this biological benefit as a result of our innovative scaffold treatments. Pilot in vivo studies and market analysis as part of this PoC will underpin future product commercialisation. Continued development of this scaffold technology has been secured through further competitive funding.
To address these issues this Proof of Concept (PoC) project extends upon on the well-established collagen scaffold fabrication technologies at the Cambridge Centre for Medical Materials. These employ an ice templated methodology to generate highly porous, homogeneous, three-dimensional scaffolds (figure 1). The particular focus of this PoC project is the development of an innovative combined cross-linking approach to enhance the structural stability of three-dimensional collagen-based structures whilst minimising reaction with cell adhesive side chains. Through this approach we are seeking to fabricate scaffolds with improved cell behaviour.
For further information: www.medical-technologies.leeds.ac.uk/
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OVERVIEW
TISSUE ENGINEERING X SYSTEMS ENGINEERING By Stuart Kay, Director, Cambridge Medtech Solutions Excellent! You’ve made good progress with the whole organ perfusion / tissue engineering protocols, and now you’re ready to proceed with the development of a more advanced bioreactor. Whether it is for on-going clinical research or it is the final system, you need to start the conversation with the systems engineers, who will add a different perspective as you all work towards a robust and capable outcome. PATHWAY FROM SOURCE TO RECIPIENT From the start, the systems engineer will want to map out the detail of the use case flow chart, which will answer the questions “What and Why and When, and How and Where and Who?” This might contain multiple starts, intersections and endpoints – for example, a biologically-derived scaffold recellularised with the recipient’s own stem cells, using
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a growth medium – and there are typically more questions than answers when first discussed. To enable this, we recommend the preparation of the outline Target Product Profile (TPP) at an early stage in the clinical research / development programme, which considers the therapy, the efficacy, how the therapy is to be deployed and used, who makes the decision to use the therapy (and based on what evidence), and what the ideal claims would be. The TPP embodies the notion of beginning with the goal in mind, and establishing it often results in a clear understanding of the regulatory pathway, and the standards and classifications that need to be met. Mapping out the pathway will also help the whole team (clinical, engineering, commercial) to visualise and develop a common understanding of what they expect and want, to challenge assumptions,
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and to identify operational constraints (tissue and fluid availability, technology availability, cost, size, weight, staffing levels, physiological limits of the therapy, and operational limits of the system). In time, this will enable the preparation of the User Requirements Specification and the Product Requirements Specification. RISK MANAGEMENT Risk assessments are not just an essential component of any system or therapy development programme – they can also be a very effective design input, and can help with the organisation of the pathway. The challenge is that many of the standard tools and techniques used are time consuming, and are based on a single snap-shot of the design. Unfortunately, this does not fit well with complex systems such as tissue engineering bioreactors
that are progressing through a rapid development programme. We favour the use of a ‘real-time’ risk assessment approach that is quick, efficient and effective. Crucially, it should also enable risk control interplay between electromechanical and software elements, and be consistent with the relevant directives and standards such as ISO 14971:2012 and IEC 62304.
systems or design iterations. Experience shows that this approach is quicker and cheaper than traditional testing, less prototypes / systems are required, less tests are carried out, but more failure modes are identified. This approach is not just limited to systems engineering and reliability engineering – it can also be used to evaluate the robustness of some therapies as well.
ADVANCED TESTING
COST
Testing is too often compromised due to the lack of samples, systems or time. It can also be compromised by only testing up to the design limits, rather than the likely operational stresses of everyday use which can combine in unexpected ways to cause a system to fail.
Reducing healthcare costs, whilst providing optimum levels of patient care, has consistently been a priority for healthcare leaders for the past few years, and is expected to continue. Whilst the health economics of the different regenerative medicine / tissue engineering approaches are yet to be fully understood, it is recognised that costs need to be aligned with mainstream healthcare reimbursement systems.
Multiple environment over-stress testing (MEOST) is a complex but powerful technique for testing combined interactions of all stresses, where the primary objective is to find the failure modes so they can be addressed. It can also be used to compare the robustness of two
Therefore, until the models can be validated, you should be pragmatic and look at every opportunity
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to reduce the costs per therapy. In our experience, the biggest savings can be achieved by avoiding expensive consumables (fluids, functional components and sensors), simplifying the design of the disposable set, avoiding the need for active thermal control during transport, and minimising the staffing resource required (peak and FTE). These are just some of the key considerations for any bioreactor system – for perfusion or persufflation; biologically-derived or synthetic scaffolds; decellularised or recellularised; whole organs or ATMP; hypothermic, normothermic or hyperthermic – and you should start considering them as early in the development process as possible. Overall, it is easier to consider these matters at the start, and to mitigate against issues that can be challenging, costly and timeconsuming to resolve later in the development programme. For more information visit: www.c-m-s.com/
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INTERNATIONAL NETWORKS
PARTNERING TO BUILD THE GLOBAL REGENMED INDUSTRY By Peter Zandstra, Chief Scientific Officer, Centre for Commercialization of Regenerative Medicine
“You have to have a big vision and take very small steps to get there. You have to be humble as you execute, but visionary and gigantic in terms of your aspiration.” So says Jason Calacanis, an American internet entrepreneur and blogger. That’s good advice for any organisation, particularly a Canadian one looking to expand beyond its borders and affect real change. The Centre for Commercialization of Regenerative Medicine (CCRM) is a 3-year-old Toronto-based notfor-profit group that is striving to be a global nexus of regenerative medicine technology and cell therapy development. As such, it is developing strategic partnerships outside of Canada to enable the sharing of intellectual property (IP) and to be a catalyst for the global translation of regenerative medicine research. “For a small, still relatively new organisation, CCRM is punching well above its weight,” declares Professor Chris Mason, University College London. “CCRM has a presence and an influence that will only grow as
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the organisation continues to make significant advances in the industry. From the UK perspective, because of its cell manufacturing technology focus, CCRM is an ideal North American partner for collaborative projects and initiatives related to getting new therapies into the clinic.” One of CCRM’s early collaboration agreements was signed with the UK’s Cell Therapy Catapult to support the development and commercialisation of RegenMed opportunities from the high impact technological discoveries emerging in their respective countries. The main targets for cell-based therapies represent high impact disease areas with significant unmet need, including oncology, heart disease, neurodegenerative diseases, musculoskeletal disorders and autoimmune diseases. The partners want to work together on suitable R&D projects, clinical trials, standardisation and regulatory efforts, as well as initiatives such as training.
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“CCRM and the Cell Therapy Catapult are both committed to moving potential therapeutic approaches from early stage research to the marketplace and there are many good arguments for combining our strengths and resources, and doing this together,” explains Dr. Michael May, President and CEO of CCRM. “If we can commercialise research faster and more effectively by partnering, then everyone benefits – especially the patient.” REGENERATIVE MEDICINE DATABASE One initiative currently underway with the Cell Therapy Catapult is the creation of a regenerative medicine company and clinical trials database that will be the world’s most comprehensive database on stem cell clinical trials. Once completed, it will be a valuable resource for industry, government and regulatory groups, scientists and patients. The Cell Therapy Catapult and U.S. groups are contributing data and support to build this valuable tool.
INTERNATIONAL NETWORKS At a technical level, another area that the Cell Therapy Catapult and CCRM are exploring is projects in the field of fundamental characteristics of pluripotent cell assay development and manufacturing. These are aspects that will benefit any commercial product emerging from these cells and thus are an ideal area for international collaboration.
facility and its pipeline of cell therapy trials with innovative technology and process development projects to build the foundation of a RegenMed/Cell Therapy global industry in Ontario. Within the Greater Toronto area alone, 25 new cell therapy clinical studies will be launched within the next 12 months.
with organisations in California, New York, Japan, Australia and the UK. Beyond CCRM’s 10+ industrial collaborations and dozens of internal projects, ongoing development projects include those focused on strategies for pluripotent stem cell expansion, cryopreservation of cell-based products and bioprocess development for the manufacture of a cellular immunotherapy to support a local Phase II trial.
If we can commercialise research faster and more effectively by partnering, then everyone benefits – especially the patient.
With a clear vision and likeminded partners, CCRM is taking the necessary steps to develop a commercial hub that will be the foundation of a RegenMed/Cell Therapy global industry to generate treatments, and potentially cures, for some of the most debilitating and costly diseases in the world.
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GOOD MANUFACTURING PRACTICE (GMP) FACILITY
Closer to home, CCRM plans to establish a global regenerative medicine industry based in Ontario that will encompass clinical trials and regulatory approval to technology development/ manufacturing and reimbursement. In partnership with both the federal and provincial governments, the University Health Network and MaRS Discovery District in Toronto, CCRM is in the process of building a stateof-the-art GMP cell manufacturing facility to serve and link other GMP facilities across Southern Ontario. CCRM intends to integrate this
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Globally, CCRM has already established IP, technology and clinical collaboration partnerships
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Peter Zandstra is a Professor at the University of Toronto’s Institute of Biomaterials and Biomedical Engineering and the Canada Research Chair in Stem Cell Bioengineering. For more information visit: www.ccrm.ca
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ACADEMIC
REGENER8’S EARLY CAREER RESEARCHERS’ NETWORK – ONE YEAR ON By Mike Raxworthy, Operations Director at Regener8
In the 2013 issue of Regen I introduced a proposal to launch a new membership stream specifically for Early Career Researchers (ECRs) working in Regenerative Medicine and Medical Technologies. Reviewing this one year on, it is clear that this has been one of the highlights of Regener8’s year – something for which those ECRs that have got involved must take the credit! Every well-run organisation needs a steering group. OK, not a statement that would meet with universal agreement but in this case those that stepped forward to form the initial steering group (from Sheffield, York, Leeds, Loughborough, Glasgow, Cardiff and Manchester) have enabled a solid start to be made and a clear course to be set. This group have been meeting every 3 months to propose and plan activities, to share information on the various opportunities available to ECRs and feedback thoughts to the Regener8 team on what would be most valued by fellow ECRs. The first major ECR event of 2014 was the “Regenerative Medicine Careers: How to choose and secure your dream career” workshop. Regener8 was delighted to complement the excellent organisation provided by the EPSRC
Centre for Innovative Manufacturing in Regenerative Medicine and cohost an event attracting a large number of ECRs to hear about career paths in industry (large companies, SMEs, start-ups), academia (technology transfer and research fellowships) and in regulatory affairs. The event also provided ECRs with a CV clinic at which feedback was contributed by mentors with industry experience. It is hoped that this event can be repeated using a similar format in 2015. A review of the workshop has been produced1 as well as an Opinion article in Orthopaedic Product News by Sophie Dale-Black2. More recently, Regener8 has set up a programme of visits to member companies. The scheme was launched in July by a visit to Smith & Nephew’s Research Centre in York. This, and the other planned visits, aimed to provide an opportunity for ECRs to pitch their work to leading companies working in the development of novel regenerative therapies and for ECRs to learn about the priorities and ways of working of these companies. Using a format that we expect to work equally well with other companies, the visit included presentations from Smith and Nephew (S&N), a tour of the Research Centre and the opportunity for networking with
References 1 http://www.epsrc-regen-med.org/news/review-of-the-first-national-regenerative-medicine-careers-event/ 2 http://www.opnews.com/article/careers-in-the-developing-regenerative-medicine-sector/#&panel1-1 3 http://www.regener8.ac.uk/latest-news/art/479/researchers-present-their-work-to-regenmed-innovators.htm
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S&N staff. Three of the party of seven were selected by Regener8 to make a brief presentation on their own current research work to S&N. One of the party, Tom Heathman from Loughborough University, observed, “It was a great insight into S&N. Touring the facilities was really useful in seeing what equipment S&N have and what they do with it, and networking with employees gives us very useful exposure and will help scope out job opportunities.” A more detailed report can be found on the Regener8 website3. We have had positive responses from a number of other member companies approached about similar visits and expect to be able to publish a programme running through to July 2015 at this year’s Regener8 conference. As we intend to keep the size of the ECR visiting group small, please do get in touch if you would like to register your interest. Further reflections on these and other events and initiatives in which Regener8 ECR members have been involved will be made from the platform during the 2014 Regener8 conference. For further information visit: www.regener8.ac.uk/
ACADEMIC
FOCUSSING ON TECHNOLOGY, INNOVATION AND THE FUTURE Technology and innovation are helping to drive the economy... but companies at the forefront of these sectors can often struggle to get their message across. Here, Samantha Davidson, managing director of marketing company Horizonworks, discusses how this can be overcome. We’ve had the pleasure of working with some truly exciting, visionary companies who have developed new technologies and made their mark on new markets. These firms can be large or small, established operators or a newlylaunched spin out, but they’ve all faced a similar challenge: to show how a complex, highly technical product or service can be used in the real world. In other words, to make it appeal to end-users in real market sectors... not just to their peers at industry get-togethers. Successfully communicating your business to an audience outside of the Regener8 conference relies on understanding your target market, getting your message right and choosing the most cost effective communications channels and tactics. Our approach to marketing will help you meet this challenge, from strategy development to implementation. We look at a business through the eyes of its staff, customers, and competitors, from which we create a marketing strategy which provides the bedrock for
growth. At the implementation stage, we take complex ideas, often underpinned by technical specifications weighed down by jargon, and translate them into clear, concise messages which resonate with end users. We then deliver this using a range of methods, including brand development, design, public relations and digital marketing. We have a strong track record in the science and technology sector: for the past four years we have been Regener8’s marketing partner, providing a comprehensive range of marketing activity, we’ve also worked with the N8 Research Partnership, Newcastle Science City and Bionow. We’ve also worked with a number of innovative companies; take Mediwikis as a case in point. The product provides medical students with free access to a collaborative revision website, effectively creating a virtual community. The site is tailored to each university curriculum and encourages the sharing of information, ideas and resources to support student learning. We supported the launch of Mediwikis into the 37 medical
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schools across the UK. Our approach included interviewing decision makers at medical schools to assess awareness of the product and this led to the product being rebranded as Mediwikis. Horizonworks then created a distinctive brand and visual identity for online and offline materials to position the product as an essential tool for the medical learning environment. Last year we worked with integrated communications company Teleware to introduce its services to the healthcare sector and raise its profile among NHS procurement personnel. This was backed by the development of a clear sales proposition by Horizonworks, and marketing collateral to support this. However you choose to innovate, Horizonworks can tailor a strategy for your business and deliver it in a way that gets results and gets you noticed. Your message is important – make sure it’s heard loud and clear by the people who matter to your organisation. For more information visit: www.horizonworks.co.uk
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COLLABORATION
THE POWER OF PARTNERSHIP By Sarah Jackson, Director of the N8 Research Partnership
This is a very exciting time for us as the N8 continues to pioneer new ways of working together and collaborating in research. One of the things I am most proud of is the way we have been able to create an environment where partners can come together to develop new ideas and novel approaches based on their complementary skills and expertise. This is when the magic happens and over the last few years, I have been privileged to see the development of some truly innovative partnerships in areas as diverse as policing research, advanced materials and of course, regenerative medicine. Regener8 has gone from strength to strength since it was started as a small research network with a handful of members in 2008. The Regener8 CV highlights a number of multi-partner innovation projects, leveraging £18m of direct and £35m of indirect investment as key achievements, not to mention assisting over 100 companies in innovation and translation activities.
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The connections that Regener8 has built between companies, academics and clinicians have helped to create commercially viable regenerative therapies and reduce their time to market. It’s extremely rewarding to see the progress many of these projects are now making in addressing some of the major health challenges we face. NEW PARTNERSHIPS DRIVE INNOVATION Joining up the talent and expertise of world class academics with industry-led R&D is a core mission of N8. By working together, universities and businesses are developing knowledge, increasing the impact of research and paving the way for new products and new technologies that not only benefit the end-user but also have a role in contributing to economic growth. The latest figures published by the Higher Education Funding Council for England (HEFCE) earlier this year, revealed that in 2012-13, the value of collaborative research
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taking place between universities and industry increased by over nine per cent – companies see the value of UK science and are investing in universities. We are proud to play a role in this story. Take the N8 Industry Innovation Forum as a good example: set up in response to industry feedback, the N8 IIF, funded by HEFCE, allows businesses to have a single conversation with eight universities around specific topic areas, and is gaining recognition for playing a vital role in bringing together new partners to generate innovative ideas for research. One eye-catching example of the kind of disruptive technology it is helping to develop is the new Open Innovation Hub for Antimicrobial Surfaces. Based at the University of Liverpool, the project emerged from the N8 IIF meeting in June 2012 which focussed on advanced materials. Microbial attack on surfaces costs the UK billions of pounds each year in product
COLLABORATION contamination, energy losses, medical infections and equipment damage. The Hub brings together academics from across the N8 universities with multinationals, SMEs and the NHS to study the behaviour of bacteria and to design and develop a new generation of intelligent surfaces and materials capable of preventing microbes from growing on surfaces and therefore inhibiting the spread of infections. One of our other successful N8 IIF projects has helped bring academics from the universities of York, Manchester, Liverpool and Sheffield together with industry partners, including Unilever, British Sugar and Croda, to identify biologicallyderived materials, manufacturing processes and technologies that can be used instead of conventional chemical-based methods. To assist in this, the group has developed an innovative Information and Knowledge Management System (IKMS) to interrogate complex data so that functional materials can be identified more quickly. This is the first of its kind to be applied across the chemical industry supply chain, and its success to date has led to a brand new side project to explore the wider commercial applications for collaborative data exploitation. SHARING KIT, SHARING SUCCESS As well as the world class expertise across the N8 universities, there is also a host of cutting edge research equipment. Sharing research equipment allows researchers to have access to the best kit possible, wherever it is located and it is already a regular part of research activity for many academics. But it can sometimes be a time-consuming or difficult process. To make it easier for universities to share equipment, we launched the N8 Equipment Sharing Toolkit earlier this year. Comprising a set of guiding principles and templates, the toolkit covers four key areas: Health and Safety; Pricing and Charging; Contracts and Legal; and VAT. Our aim is that the toolkit will support universities to work collectively and react quickly and efficiently to opportunities for new capital investments. It has already been used to develop a co-ordinated family of bids to the Engineering and Physical Sciences Research Council (EPSRC) Core Chemistry Capability initiative. This major investment has now enabled us to
install some of the latest and most powerful scientific instruments in the N8 universities, supporting worldclass research in areas as diverse as drug development, industrial biotechnology and quantum computing. LEADING THE WAY IN COLLABORATION Two years ago, Sir Alan Langlands addressed the Regener8 conference in his role as Chief Executive of HEFCE; I am delighted that he does so again, this time as Chair of the N8 Research Partnership and Vice Chancellor of the University of Leeds. His outstanding leadership, and the new thinking
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and commitment of the Pro-ViceChancellors are proving pivotal in keeping us at the forefront of collaborative research. Our universities are playing a major role in creating competitive advantage through collaboration, co-operation, and co-creation, and the N8 has led the way in this by bringing together the best with the best and starting new conversations. This creates the right environment for innovation and game-changing ideas that can deliver success for businesses, the economy and society. For more information visit: www.n8research.org.uk
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NETWORKS
FIVE YEARS OF SUCCESSFUL RESEARCH TRANSLATION AND COMMERCIALISATION By Ceri Williams, Director of Operations, Medical Technologies Innovation and Knowledge Centre (IKC)
Over the last five years the Medical Technologies IKC has been building the vital relationships and collaborations that lead to successful innovation. We’re now seeing the natural progression of these relationships, with a pipeline of Proof of Concept projects developed between academics, clinicians and industry partners, and spin-out companies formed to commercialise new medical technology products and services. Quantum Imaging (our first IKC spin-out) is a great example of how our management practice has engendered investor confidence and attracted significant venture capital investment in a start-up company. It demonstrates how the projects we support are reaching Technology Readiness Level 5 - where investors have the confidence to invest in new emerging technologies and progress them all the way to launch on the market. We’re widening our reach throughout the UK and have established the
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Medical Technologies IKC as a national centre. We now have nine Proof of Concept projects in progress with national university partners. Our strategic alliance with Regener8 has played a key role in this, widening reach for both the IKC and Regener8. The innovative practice and culture that we’ve nurtured and developed at the Medical Technologies IKC is now being embedded in universities around the UK. This is producing a change in how researchers – both early career researchers and seasoned academics - think about the translation of research to reach a defined commercial application. The field of regenerative medicine is a key priority for the government in order to ensure that the needs of a growing ageing population can be managed in a cost-effective way and deliver good quality of life for longer – 50 active years after fifty®. We’ve focused on the regenerative device sector as technologies in this field can be translated to full commercially available products more quickly and cost-effectively. The IKC is moving
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regenerative medicine technologies closer to commercialisation and delivering benefits to patients. Through developing platform technologies that are suitable for licence agreements to develop second generation technologies, the IKC also continues to support our spin out companies such as Tissue Regenix Group plc - working with tissue decellularisation technologies - and Credentis ag, which develops self-assembling peptide scaffolds used in dental treatment. We have also formed other strategic collaborations such as a Memorandum of Understanding with the Cell Therapy Catapult (CTC), which focuses on the development of the UK cell therapy industry. The regenerative medicine strategies supported by the CTC complement our approach which uses the medical device regulatory pathway to develop regenerative devices. Plans are now being developed to identify collaborative opportunities for the IKC and CTC to work on technologies such as acellular scaffolds for the
NETWORKS delivery of cellular therapies. This initiative, led by Regener8, has the potential to involve academic, clinical and industrial members of Regener8, the IKC and the CTC to support the successful translation of research. As a result of this partnership with Regener8, an open call was made to identify projects in hard and soft tissue repair using acellular scaffolds, as well as other regenerative technologies, which could be developed further. From the 14 applications received, two have been awarded Proof of Concept funding. In addition, key groups in UK centres of excellence for acellular technologies were identified and a further seven UK universities have been awarded funding for translational projects. Through these initiatives we will accelerate and enhance innovation between academic and industry collaborators in national projects that have significant commercial potential and bridge the innovation gap between research and commercialisation.
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The innovative practice and culture that we’ve nurtured and developed at the Medical Technologies IKC is now being embedded in universities around the UK
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We have achieved some significant commercial success: a portable heart scanner, developed by Professor Ben Varcoe and supported by the Medical Technologies IKC, has secured £1.6million start-up investment to bring it closer to commercialisation. Working with the University of Leeds’ commercialisation partner, the IP Group, the IKC helped to set up a spin out company, Quantum Imaging Ltd, in February 2014. This will enable a CE-marked commercial device to be developed and the necessary approvals to be obtained, so larger scale trials can be conducted.
We have contributed to the development of 46 new products that have reached the market, and to date the IKC academic base has secured £84m investment in collaborative research funded by the public sector, and a further £12m direct investment from industry. In addition the start-up companies that have been developed on IP generated through the IKC have together secured £57m private sector investment in their future development to fully commercialise their products based upon our IP and technology.
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In summary, after five years the Medical Technologies IKC is proud to be recognised as a successful national research translation and commercialisation centre. Our work will continue to reinforce and grow this reputation nationally whilst we continue to create value from novel approaches to addressing clinical needs and assist the transition of research from fundamental to translational, for the benefit of the nation’s health and wellbeing. For further information visit: www.medical-technologies.leeds. ac.uk/
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CASE STUDY
URINARY TRACT APPLICATION FOR A BLADDER-DERIVED NATURAL ACELLULAR MATRIX
By Anna Radford and Professor Jenny Southgate, Jack Birch Unit of Molecular Carcinogenesis, Department of Biology, University of York The treatment of a common condition affecting the urinary tract in young boys could be permanently resolved by implanting tissue which integrates well and supports the child’s own tissue. Hypospadias is a congenital abnormality affecting 1 in 300 young boys. It is characterised in part by abnormal placement of the urethral opening, which can occur anywhere from just below the end of the penis to the scrotum. The condition often requires multiple or “staged” surgical correction because the patient’s own tissue is inadequate in quantity and quality. This may frequently lead to complications requiring further reconstructive surgery. There is a clinical need for an effective method by which enough material is implanted at the primary stage of repair to reduce the complication rate. This is being addressed in a Proof of Concept project led by Professor Jenny Southgate (University of York) in collaboration with others at the University of Leeds. The collaboration
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had previously developed a porcine decellularised bladder biomaterial as part of a BBSRC-funded project and evaluation in a BBSRC follow-on grant indicated the potential for using the natural decellularised matrix for homologous use in urological surgery. The next stage, for which PoC funding was requested, was to test the material’s use and functionality in a large animal model. The biocompatibility and integration of the new material is being compared to that of a commercially available product. This commercial product has been reported in the “off-licence” surgical treatment of complex hypospadias by Mr Ramnath Subramaniam, the surgeon co-investigator on the project, who is based at the Department of Paediatric Urology, Leeds Teaching Hospitals Trust. However the host response to such material is unknown and it is believed that the York/Leeds biomaterial will be more suitable due to its better structural features and retention of biological properties as a result of not being cross-linked.
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The implanted biomaterial will be for homologous use, meaning that it will be derived from and used in the urinary tract for which it was evolved, leading to a better, faster surgical repair and an improved outcome for the patient. The York/Leeds team are collaborating with two partners, Tissue Regenix and NHS R&D, with a view to moving forward to clinic with either the porcine acellular matrix or a version derived from human bladder tissue. The Medical Technologies IKC funding was crucial to the development of this project. By providing funding to prove the concept, the potential risk for industry partners is ameliorated. This biomaterial has potential to make a real difference to the lives of many patients and the funding is facilitating a critical step in the translation of a promising research finding from the laboratory to the clinic. For further information visit: www.york.ac.uk/biology/jack-birchunit
CASE STUDY
SMALL BOWEL REPLACEMENT AND REGENERATION By Tahera Ansari, Northwick Park Institute for Medical Research Bowel disease leading to nutrient absorptive failure is a significant clinical issue, ultimately leading to shortened life expectancy, poor quality of life and reliance on chronic care regimes with major comorbidities and significant impact on NHS finances. This project aims to develop a product to replace diseased small bowel tissue and restore normal function through the combination of decellularised porcine bowel with mesenchymal stem cells. The aim is to avoid the ATMP regulations by seeding acellular bowel scaffold grafts at the time of implantation into the patient. Autologous mesenchymal stem cells would be prepared with minimal manipulation and then reseeded on to the scaffold and use the patient as the
‘bioreactor’. Essentially, the strategy is to grow the organ in the body until differentiated/regenerated enough to be surgically placed ‘on-line’ with a second surgical procedure. The main outcome of the project will be 1) the degree of scaffold and vasculature priming/ seeding achieved prior to in vivo implantation, and 2) the development of an implantation model translatable to first in man clinical phase. [For human implantation either a human small bowel scaffold (allogeneic; of cadaveric origin) or a porcine derived scaffold will be used in combination with human autologous cells.] Whilst it is recognised that in the preclinical animal models using a porcine scaffold in a porcine implantation model is an allogeneic
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use compared to the proposed clinical use of a xenogeneic porcine scaffold into a patient; the porcine bowel large animal model remains the best representation of the human condition and surgery. Previous work in this lab and others, has demonstrated that data generated from acellular porcine scaffolds implanted allogeneically into porcine models is translated into human clinical safety and performance. Therefore, the current proposal of using an allogeneic implantation model with autologous cells is warranted. Taken together, this data will be pivotal to raise additional private investment to commercialise the technology. For further information visit: www.npimr.org
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CASE STUDY
MANUFACTURING BONE TISSUE USING RESORBABLE CALCIUM PHOSPHATE MICROSPHERES LOADED WITH AUTOLOGOUS STEM CELLS: By Ifty Ahmed, Faculty of Engineering, University of Nottingham. Osteoporosis is a chronic, progressive bone disease in which bone resorption exceeds bone formation, leading to a reduction in bone mineral density and disruption of bone microarchitecture. This progressive loss of bone mass causes the bones to become more fragile and break easily, and is especially prevalent for bones of the hip, spine and wrist. Nearly 20 million people are aged 50 years and over in the UK, which is predicted to increase to 25 million by 2020. Over 60,000 hip, 50,000 wrist and 120,000 vertebral osteoporosis-related fractures occur each year in the UK. Recent trends suggest that hip fracture rates will increase to 117,000 by 2016 and the combined cost of hospital and social care for these patients amounts to more than ÂŁ1.73 billion per year in the UK alone. Fragility fractures are a disabling pathology and there is a significant clinical need for new improved methods of bone regeneration and repair, especially for an ever-increasing ageing population. There has been a major shift in emphasis from tissue repair to tissue regeneration as a solution to the ever-growing need for long-term orthopaedic care. Preliminary proofof-concept studies have successfully demonstrated that manufacture of resorbable amorphous calcium phosphate (CaP) bulk glass microspheres was not only entirely feasible but also (and more importantly for biomedical applications) successful manufacture of CaP porous microspheres has also been achieved (see Figure 1). The main advantages for this technology are: 1) the degradation profiles for these amorphous CaP microspheres can easily
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be tailored (from days, weeks to several months), 2) these glasses can easily be doped with osteoporotic positives such as strontium to inhibit bone resorption, 3) the porous microspheres can be loaded with biological components (i.e. autologous stem cells) in order to provide a potent combinatorial effect of bone repair and regeneration for treatment of osteoporosis, and 4) can provide a minimally invasive delivery route through simple mechanisms such as syringes or cannulas. Minimally invasive procedures for bone repair and regeneration offer many benefits such as reduced trauma, especially for elderly patients. Microspheres have the potential to encapsulate cells and many types of drugs including small molecules, nucleic acids, proteins etc and can be administered easily through a syringe needle. Encapsulated components can then be released at controlled rates for relatively long periods of time. Such systems offer many advantages over traditional methods of administration: 1) drug
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or biological component release rates can be tailored to the needs of a specific application; 2) these systems can provide protection of drugs, especially proteins that would otherwise be rapidly destroyed by the body; and 3) can increase patient comfort and compliance by replacing frequent (e.g. daily) doses with infrequent injections. To enable commercial realisation for this technology, the research team at Nottingham (which includes Professor David Grant, Dr Virginie Sottile and Professor Brigitte Scammell) are currently pursuing follow-on studies to investigate development of a prototype delivery device, further manufacturing scaleup, IP development and pre-clinical trials. Figure 1: a) Initial ground bulk calcium phosphate (CaP) glass particles; b) bulk CaP microspheres; c, d, e and f) examples of porous CaP microspheres manufactured. For more information visit: www.nottingham.ac.uk/engineering/ people/ifty.ahmed
NEWCASTLE CELL THERAPIES
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SPONSORS
REGENER8 2014 SPONSORS Asymptote Supplies and develops innovative cryopreservation and freeze drying equipment and consumables. www.asymptote.co.uk BioPharma Process Systems The UK’s foremost provider of freeze drying equipment and services, including equipment maintenance, R&D, characterisation and training. www.biopharma.co.uk/biopharma-process-systems/home/ Cambridge Medtech Solutions An independent technical and strategic consultancy for the design, development and industrialisation of commercially successful medical devices and enabling technologies. www.c-m-s.com/ Cytori Cytori is a world leader specializing in the development of medical technologies that enable physicians to use the human body’s resources, such as adult stem and regenerative cells from adipose tissue, for clinical benefit. www.cytori.com Electrospinning Co Utilising the world-class electrospinning platform at the Rutherford Appleton Laboratory in Oxfordshire, UK to develop and manufacture highly consistent fibres for incorporation into easy-to-use scaffold products. www.electrospinning.co.uk Fluidigm Fluidigm is a biotech tools company that creates microfluidic-based chips and instrumentation for biological research. www.fluidigm.com/home.html Horizonworks Horizonworks is a full-service marketing company, offering strategic marketing, public relations, design, brand development and digital marketing. We’re experts in life sciences, biomedical and technology sectors and specialise in translating technical information into marketing messages which set our clients apart. www.horizonworks.co.uk Intertek Conducts analysis and certification of regenerative medicine products to ensure the quality and dafety of products. www.intertek.com
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SPONSORS
Medical Technologies IKC Medical Technologies IKC facilitates collaboration between companies, engineers, scientists and clinicians to develop innovative technologies that help the body repair and restore function. www.medical-technologies.leeds.ac.uk/ Newcastle University Cellular Therapies Facility The Cellular Therapies Facility at Newcastle University is an MHRA-licensed clean room complex designed specifically for the production of cellular therapies. It is one of the biggest such facilities in Europe, making Newcastle the ideal place to manufacture cellular therapies for translational clinical research. www.ncl.ac.uk/ctf NHS Blood and Transplant Special Health Authority dedicated to saving and improving lives through the wide range of services we provide to the NHS. Our purpose is to save and improve lives. www.nhsbt.nhs.uk NPD Consultants Experts in new product development with proven experience of delivering complex projects across the life science and medical device sectors. www.npdconsultants.co.uk/index.htm Peprotech World leader in supplying high quality cytokine products. www.peprotech.com Quest Biomedical Limited A leading distributor of diagnostic tests and other products into the United Kingdom and Republic of Ireland laboratory markets. www.questbiomedical.com Source Bioscience Source BioScience specialise in the simulation of environmental conditions and providing equipment and services designed to solve specific environmental testing and storage needs. www.sourcebioscience.com Spheritech Specialists in the development and manufacture of polymers for a range of applications in biotechnology and healthcare. www.spheritech.com
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OVERVIEW
MEMBER BENEFITS MEMBERSHIP BENEFITS
E-NEWSLETTER
Membership of Regener8 is free and it’s easy to sign up. Regener8 members benefit from the following:
Our regular e-newsletter contains news and events from members and the wider regenerative medicine community and is distributed to over 900 named individuals. If you’d like to receive the Regener8 enewsletter you can sign up via the website, or email regener8@horizonworks.co.uk.
ACCESS TO WORLD CLASS TECHNOLOGY Regener8 has close links with other networks across the UK and with the N8 Universities (Durham, Lancaster, Leeds, Liverpool, Manchester, Newcastle, Sheffield and York), research institutes and clinical centres of excellence in regenerative medicine throughout the UK.
REGEN MAGAZINE Regen is the annual magazine for Regener8 members and the wider regenerative medicine community. Copies are distributed to named industry, clinical and academic representatives and it is also available online on our website. Advertising packages are available.
EARLY CAREER RESEARCHERS’ NETWORK This year Regener8 launched a new membership stream for Early Career Researchers (ECRs) working in Regenerative Medicine and Medical Technologies. The group meets on a quarterly basis to propose and plan activities, share information on various opportunities available to ECRs and feedback thoughts to the Regener8 team on what would be most valued by fellow ECRs. To be part of this network ‘Like’ the Facebook page at www.facebook.com/ regener8ECRnetwork
MEMBER EVENTS The online events calendar on the Regener8 website is regularly updated with events that we think will be of interest to the regenerative medicine community. ANNUAL CONFERENCE
REGENER8 WEBSITE
We hold an annual conference, featuring respected academic, clinical and industry speakers from the translational regenerative community. Now established as one of the leading RegenMed events in the UK, the Regener8 Annual Conference offers networking and sales opportunities through the exhibition packages available.
The Regner8 website www.regener8.ac.uk typically attracts over 1,000 unique visitors per month and has referrals on key partner websites. Regener8 members are featured on the Regener8 website with a profile, logo, web link and contact details. Regener8 members can update and edit their personal or organisation details at any time by simply logging in to the site. Regener8 members can also post their own news and events to the website. The site also features a fully searchable Expertise Directory to find Regener8 members by location and area of expertise.
MARKETING AND PR OPPORTUNITIES Members can share their news on the Regener8 website, through the e-newsletter and in regen magazine. Members can also work with Regener8’s preferred marketing and PR partner, Horizonworks, who can provide advice on all areas of marketing including strategy, branding, design, communications and PR.
COLLABORATIVE PROJECTS Regener8 works with members to identify specific projects, form consortia and broker funding. In some cases we can project manage where appropriate.
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For more information and to sign up as a Regener8 member, visit: www.regener8.ac.uk
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Regener8, X102 Medical and Biological Engineering, University of Leeds, Leeds, LS2 9JT E: regener8@horizonworks.co.uk Contact details for key members of the Regener8 team can be found on our website at
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www.regener8.ac.uk