Regen magazine

The regenerative devices community magazine

issue 08 2017

med-tech@leeds.ac.uk

The regenerative devices community magazine

Taking on the giants Rules of engagement Injectable paste tackles deep bone infection

issue 08 2017

regen.

c/o Institute of Medical and Biological Engineering, University of Leeds, LS2 9JT +44 (0)113 343 0923

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Regen. Magazine 2017

Contents 03

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INTRODUCTION Ten pillars of innovation wisdom

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IKC & Regener8 in numbers

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A leading role in translating research

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NATIONAL PERSPECTIVES Taking on the giants

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Making the case for adoption

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INNOVATION & GROWTH Harvesting fat cells to repair anastomotic leaks

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Injectable paste tackles deep bone infection

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A chemical solution to sterilising implants

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Plugging the gap

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Dual matrix scaffold provides better support

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Translation through collaboration

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Arthroscopic brush can promote stem cell healing

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New heart scanner offers detailed, rapid assessment

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Innovative partnerships to tackle unmet clinical need

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COMMUNITY

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Rules of engagement

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Widening markets, extending reach, growing capability

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Community tweets

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Supplying new skills to a growing industry

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INTRODUCTION

Ten pillars of innovation wisdom When IKC began in 2009, our mission statement laid out what we planned to do to help build a £1bn regenerative devices sector in the UK. Now, eight years on, as a mature organisation well into our second phase of funding, we can confidently talk about what we do, what we’ve achieved and what work is already underway to attain that goal.

Some 279 PhDs and post-doctoral researchers have benefitted from our training programmes in medical technology innovation, an excellent example of ‘developing skills to help people and businesses thrive’ (pillar 2). Through our Translate programme, we’re also providing advice, mentoring and support for academics, to help them develop and commercialise medical technologies.

It’s been enlightening and gratifying to see how much of this is reflected in the Government’s proposals for an Industrial Strategy, laid out in their recent Green Paper. The first of the strategy’s ten ‘pillars’ – science, research and innovation – focuses on commercialisation of the UK’s world-leading science base to drive economic growth, which is, of course, IKC Regener8’s core purpose.

With 84 of our projects and technologies progressed to Technology Readiness Level 5, 32 patents filed and six spin-outs created, we can also confidently claim to be ‘supporting businesses to start and grow’ (pillar 3). These technologies have helped to ‘encourage investment’ (pillar 6), with £118m private sector investment resulting directly from IKC Regener8 activities, plus a further £30m of indirect investment.

Many university research organisations will see their activity link to this first pillar, but we’re fairly unusual to have so many of the other pillars relate equally closely to our work.

The Medical Technology Science and Innovation Audit that we’re undertaking on behalf of BEIS will provide an evidence base

PROFESSOR JOHN FISHER CBE

for further activity to ‘cultivating this worldleading sector’ (pillar 8).

Our work is helping to ‘drive growth across the whole country’ (pillar 9), particularly in helping to build a strong medical technology base in the Leeds City Region. Leeds has recently seen a new manufacturing facility opened by Tissue Regenix and a £20m capital EMEA technology development campus by DuPuy Synthes, sustaining 500 high value jobs.

There is also a clear match with the final pillar of the industrial strategy: ‘creating the right institutions to bring together sectors and places’.

With IKC and Regener8 joining forces, we are building a medical technology community, spanning academics, clinicians and industry, to ensure that the right partnerships come together to help progress specific projects and support the growth of the sector.

Professor John Fisher CBE Academic Director, Medical Technologies IKC

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Regen. Magazine 2017

IKC & Regener8 in numbers

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INTRODUCTION

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A leading role in translating research We’ve entered an exciting phase of IKC Regener8 where we’re taking a national leadership role in translating medtech, developing capability and spreading good practice to a wider range of partners than ever before. We began with 50 academic partners, but eight years on, that’s grown to 86 partners across 35 universities.

IKC Regener8’s goal is to develop technologies to the stage where they offer a sound financial opportunity to potential investors. Our distinctive contribution to this is not simply proof of concept (POC) funding; it’s equally – if not more – about practical support.

Underpinning our success is the specialist knowledge and expertise of our Technology Innovation Managers (TIMs) in bringing the right parties together, and in developing and managing medtech projects.

When an academic approaches IKC Regener8 with a technology opportunity, the chances are there will be unanswered questions.

For example, what is the technology capable of delivering and is there freedom to use it in the way the academic is suggesting?

Could it address a real clinical need?

Are the right partners involved to develop the technology effectively?

DR JOSEPHINE DIXON-HARDY

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INTRODUCTION

A COMPANY’S ACTIVE INVOLVEMENT IN A PROJECT IS CRUCIAL TO DEVELOPING IDEAS AND DRIVING THEM FORWARD, WHICH IS WHY WE’VE ADOPTED THIS ‘INDUSTRY INSPIRED, ACADEMICALLY LED’ APPROACH.

Applications for funding often succeed or fail with little or no feedback from the funder – which means there is no learning for the parties involved. Our TIMs work with the academic to answer these questions, in an iterative process that improves the chances of a successful grant application. Crucially, this ‘action-learning’ process also develops the academic’s capability to bid for next-stage funding or investment, whether that’s from, for example, the National Institute for Health Research, the Medical Research Council, a company or an investor.

Our current funding call brings the essential commercial development insights of medtech companies to the table and ensures that the needs of the industry are addressed.

A company’s active involvement in a project is crucial to developing ideas and driving them

forward, which is why we’ve adopted this ‘industry inspired, academically led’ approach.

We’ve also introduced what we call ‘waves’ of POC applications with staggered deadlines.

This creates an environment in which academics have time to work with our TIMs and ensure all the essential elements are in place before submitting full proposals. It’s testament to the dedication and ability of our TIMs that they’ve pioneered this more intensive – but educationally more effective – approach.

The structure of our external partnerships is evolving too. Forging strong working relationships with different types of organisations allows both parties to learn from each other and our joint project programme with Arthritis Research UK is a great example of this (see page 19).

More recently, we’ve been passing on our skills and experience in connecting, facilitating and supporting medtech translation to Leeds City Region partners through the Translate programme, which you can read about on page 24.

Our approach is constantly evolving in response to a regulatory framework that’s becoming ever more rigorous and challenging.

It’s only through refining and testing our processes and mechanisms, seeking feedback from our partners and applying our learning that we can ensure our continued success.

Dr Josephine Dixon-Hardy, Director of Medical Technology Innovation Medical Technologies IKC

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National perspectives In a constantly shifting regulatory and technological landscape, we need to work even harder to get innovative products market-ready.

Sharing expertise and gaining insights from colleagues in industry and from within the health and care sector helps us to ensure projects are designed with the best chance of meeting market need, gaining regulatory approval and being adopted within healthcare systems.

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NATIONAL PERSPECTIVES

Taking on the

giants

Leeds-based company, Arterius, is preparing to take on industry giants with its nextgeneration bioresorbable coronary stent.

Led by polymer chemist Dr Kadem Al-Lamee, the company’s ultra-thin, ultrastrong stent is the result of combining his 30 years of R&D experience with observing developments in the market and knowing what improvements cardiologists are looking for. It’s also testament to a steadfast determination to overcome design and process challenges through a series of smart choices in university collaborators.

The ArterioSorbTM stent is expected to reach a first-in-man clinical trial in Q3 of 2018, having passed pre-clinical tests with flying colours. Its construction is remarkable. Made from polylactic acid (PLA), its walls are just 95 microns thick – finer than an average human hair – compared with the 157 micron thickness of the market-leading product. Its manufacture uses an adaption of a die drawing technique originally developed at the University of Bradford for producing gas pipes, with the production process significantly increasing the material’s strength. The result is the thinnest and strongest non-metallic bioresorbable stent in the world – and independent tests back this up.

Dr Al-Lamee says the secret to its performance is also in the design: “All bioresorbable scaffolds are a mesh of some form, but we’ve dedicated a great deal of time to perfect a unique open-cell design, which can be crimped very tightly to the catheter in a spiral system to make insertion into finer arteries easier. When expanded, the central cells’ shape supports the most diseased part of the artery, then the individual cells increase in size towards each end to enable better flexibility.”

DR KAMDEM AL-LAMEE, CEO, ARTERIUS

competitors, but Dr Al-Lamee has no fear of going head-to-head with them.

“It’s a very exciting time for us. Our product is superior, cheaper and we can manufacture in-house if we choose to. Our patents are in place. We’ve got experienced management to take Arterius forward and first class pre-clinical and clinical support. The most frustrating part has been the timeframe; our competitors have thousands of staff working on their products and spend many millions in developing them.

“We’re a small team and have had to wait to secure investment and win grants from Innovate UK to move forward. But I strongly believe that with the right ideas and the right partners – our relationships with the Universities of Bradford and Southampton have been crucial to reaching this point - it’s entirely possible for a small medtech company like ours to compete against the giants.”

He’s seen many companies attracted to the $10 billion global stent market, only to fold or withdraw leaving a handful of major league

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Making the case for

A positive recommendation from the National Institute for Health and Care Excellence (NICE) is the most crucial step towards getting a new medical technology adopted in the NHS. Deborah Morrison, Senior Scientific Adviser at NICE, outlines some of the services available for early stage medical technology companies pursuing this aim.

GETTING THE HTA ADVICE EARLY ON IS BECOMING INCREASINGLY IMPORTANT SO THE SYSTEM CAN

For many companies and organisations, the first point of contact at NICE will be through the Office for Market Access (OMA), where the company can receive advice on the best way to guide their product through NICE processes.

NICE requires a rigorous approach to evidence generation to support the case for adoption of a new product into the NHS. This often extends beyond requirements for the CE marking process to show EU compliance. Because of this, we offer detailed guidance through services such as bespoke consultation with NICE experts and NICE Scientific Advice.

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MAXIMISE THE CHANCES OF EFFECTIVE NEW TECHNOLOGIES ENTERING THE HEALTH SERVICE SOONER AND BRING BENEFITS TO PATIENTS.

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NATIONAL PERSPECTIVES

DEBORAH MORRISON

These are generally three-hour sessions, which give organisations the opportunity to present plans and get detailed recommendations about their product development pathway. NICE Scientific Advice also offers a light advice service to small companies which is faster and offers a teleconference with the company instead of a face-to-face meeting.

This year, NICE is launching a new online service, the Medtech Early Technical Assessment Tool (META). Product developers will answer a structured set of questions about their technology and evidence available to date for the META process to assist them with identifying gaps in evidence required for a Health Technology Assessment (HTA). HTA is the framework within which NICE evaluates new technologies. META is an affordable way to assess product development plans, get advice on refining a value proposition and identify areas where more clinical or economic evidence is needed.

Some of the organisations using this service are at quite a late stage in product development, and just want to check if they’ve done enough to take it forward to a HTA, whereas others are at a much earlier stage, and still struggling to articulate their product’s value proposition.

This has had a particular impact on digital health technologies, for example, where some apps are now being classified as medical devices because they influence treatment decisions and so they need a different standard of approval which may cause a delay in adoption into clinical practice.

Once an organisation has completed its product development and assembled sufficient evidence, they can submit the technology into one of NICE’s HTA programmes. Most commonly this will be the Medical Technologies Evaluation Programme. Only around 16 per cent of the products submitted are selected for this process, as NICE is looking for transformative technologies that offer clear benefits and whose value proposition is supported by high quality evidence.

Getting the HTA advice early on is becoming increasingly important so the system can maximise the chances of effective new technologies entering the health service sooner and bring benefits to patients.

Deborah Morrison Senior Scientific Adviser, NICE

A smaller percentage have been selected and routed to the NICE Diagnostics Assessment Programme or the Technology Appraisals programme.

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Innovation & growth Our vision is to see the UK regenerative devices sector grow to be a £1bn per year industry by 2025. With 84 of our technologies reaching Technology Readiness Level 5, we’ve already taken some huge strides towards realising that vision.

A sustainable pipeline of innovation is crucial to its success, however, and our projects span the Technology Readiness scale, from emerging technologies to those which are now much closer to market.

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INNOVATION & GROWTH

A method of harvesting patients’ own fat cells and using them during colorectal surgery to promote healing is being investigated by researchers at the NIHR Healthcare Technology Co-operative (HTC) in Colorectal Therapies, in partnership with the IKC and the regenerative cell therapy company, Cytori Therapeutics Ltd.

“Anastomotic leak is always a risk in colorectal surgery and is one of the unmet clinical needs that the HTC is aiming to address,” explains Professor Jayne. “When Cytori approached us, we quickly saw the potential for partnering with them to tackle this challenge. It’s an approach with huge potential not only for gastrointestinal surgery, but also for wound healing generally.”

Surgery is the main treatment for colorectal cancer. Cancerous cells are removed from the bowel, and the two sections are re-joined in a process called anastomosis. When the anastomosis does not heal properly, however, a leak can occur – a complication that can be dangerous for patients and can require additional surgery. Unfortunately, despite advances in surgical technology, the rate of anastomotic leak has not changed and still occurs in between two and ten per cent of cases, depending on the type of surgery performed.

In the first phase of the project, the team was supported by an IKC translational feasibility grant, which enabled them to use specialist equipment loaned by Cytori to extract the cells and characterise them in the laboratory. This phase was also funded through Professor Jayne’s NIHR Research Professorship.

Led by Professor David Jayne, Clinical Director of the HTC, the team is developing a technique to promote anastomotic healing using fat taken from the omentum, a piece of fatty tissue inside the abdomen.

This tissue is rich in regenerative cells that help to promote tissue healing. These can be harvested during surgery, and mixed with a rapidly solidifying gel, developed in collaboration with Dr Olivier Cayre at the University of Leeds’ Faculty of Engineering.

The gel is applied around the anastomosis at the time of surgery where it sets, holding the cells in place and enabling them to promote healing.

Over the next year, the team plans to test the gel in animal models of anastomotic leak before pursuing regulatory approvals and a first-in-man trial.

ANASTOMOTIC LEAK IS ALWAYS A RISK IN COLORECTAL SURGERY AND IS ONE OF THE UNMET CLINICAL NEEDS THAT THE HTC IS AIMING TO ADDRESS.

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Injectable paste tackles deep bone infection THE TECHNOLOGY The first injectable paste that can both promote bone healing and combat infection is being developed in a partnership between the University of Sheffield and biomaterials manufacturer, Ceramisys.

Made by modifying a nanoscale calcium phosphate base material, the paste can be used to prevent deep bone infections that might occur around a failing device, such as a hip replacement, as a result of injury or following surgery.

Although injectable bone pastes have been commercialised before, this is the first time a material has been developed that can combine enhanced bone tissue healing and anti-microbial properties to tackle a wide range of infections.

Using a translational feasibility grant from the IKC, Sheffield researchers led by Dr Cheryl Miller and Professor Paul Hatton in the School of Dentistry, worked with Ceramisys to optimise the ‘recipe’ for the paste and to test it using the University’s material characterisation and tissue culture facilities.

PROFESSOR PAUL HATTON

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INNOVATION & GROWTH

THE PEOPLE Our Technology Innovation Managers work closely with researchers to identify and develop medical technologies with the most promising commercial potential.

Often this will involve collaboration with both early career and senior researchers to design and guide projects.

We asked the experts developing this project what contributed to its success.

RESEARCH SUPERVISOR, PROFESSOR PAUL HATTON “When researchers are at that early stage in their careers, they’re often already great scientists who have made some important contributions, but they have rarely seen those translated. It’s a huge plus to be involved in a programme that lets people take their most exciting and translatable science and set out on that journey.

“Once projects reach the proof of concept stage, the IKC makes sure researchers get really high quality critical feedback so that even when projects aren’t successful, there is genuinely useful advice on how to improve the proposal – and the project. I would really like to see other funding organisations contributing tailored programmes for ECRs and maybe that’s something the IKC could help lobby for.”

DR CHERYL MILLER

TECHNOLOGY INNOVATION MANAGER, DR JENNY SPEAR “ The nano-hydroxyapatite bone filler project is a great example of the IKC’s translation pipeline in action. We worked really closely with Cheryl and her team from early on in the project, including helping the team secure a grant from the IKC’s translational feasibility fund to get the research ready for a proof of concept application.

“It can be a real challenge for researchers to kick-start their independent funding portfolio.

At the IKC we have the ability to provide professional innovation support to projects, to enable promising researchers the opportunity to access feasibility and POC funds. What I really like about the application process for the translational feasibility fund was that it was anonymised, so projects were assessed purely on merit.”

RESEARCHER, DR CAROLINE WILCOCK “ Deep bone infection can be difficult to treat successfully; it can be very painful for patients, as well as keeping them in hospital for long periods. There’s a lot of pressure on device manufacturers to come up with solutions.

DR JENNY SPEAR

“I worked with Cheryl Miller and Paul Hatton on the translational feasibility work which was supported by the IKC. That work enabled us to progress the research towards a proof of concept project, as well as giving our researchers valuable experience of working with an industrial partner. I’ve gained a lot of experience of industrial and manufacturing processes that will be useful in many future projects.”

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IT WILL BE VERY REWARDING

A chemical solution to sterilising implants TO SEE SURGEONS BEING

ABLE TO USE THIS PRODUCT – HOPEFULLY IN THE

NEXT COUPLE OF YEARS.

A way of sterilising decellularised material so it can be safely implanted into patients is being tested by researchers at the University of Leeds. Working in partnership with NHS Blood and Transplant (NHSBT), the team is investigating the potential for a chemical sterilant that will kill bacteria in bonetendon-bone implants without reducing the mechanical strength.

The project, led by Professor Eileen Ingham and supported by the IKC, is the final step in the development of decellularised bonetendon-bone implants, which can be used to replace ruptured anterior cruciate ligaments.

The decellularisation process is lengthy and complex, and the risk of contamination is significant, so an effective way to sterilise the material is a crucial part of the process.

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The team has been working with NHSBT over a number of years to develop the decellularisation process which has now been tested for use in bone-tendon-bone implants and in human dermis. The sterilant solution developed at NHSBT, is a mixture of hydrogen peroxide and copper chloride, and it has already been shown to work in skin tissue.

To find out if it would also work in tendon tissue, NHSBT once again approached Professor Ingham’ s team.

Paul Rooney, Research and Development Manager for NHSBT Tissue and Eye Services, explains: “It’s possible to sterilise some tissues by irradiating them, but we know that this can reduce the structural strength of tendon material, so we needed to find another solution. This chemical sterilant does kill bacteria very quickly in decellularised dermis, and it’s a promising way forward for treating bone-tendon-bone implants – and possibly a range of other decellularised materials too.”

Professor Ingham’s team is carrying out tests on tissue samples implanted with bacterial spores to find out how long they should remain in the sterilant before the levels of bacteria are sufficiently reduced. They’ll then test batches of sterilised tissue samples to see if they retain their mechanical strength.

If these results are positive, NHSBT will be able to incorporate the process into a Good Manufacturing Practice (GMP) protocol for producing decellularised tendons, which will pave the way for clinical evaluations.

“It will be very rewarding to see surgeons being able to use this product – hopefully in the next couple of years,” says Professor Ingham. “Obviously this part of the project is absolutely key to that, because it’s about patient safety. We need to be sure that the sterilisation methods are effective, and that the most important biomechanical properties have not been changed during the process.”

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Plugging the

A new decellularised scaffold for use in urology enables greater infiltration of cells in comparison to existing materials.

Made from full-thickness porcine bladder, PABM (porcine acellular bladder matrix) is a natural biomaterial with both strength and flexibility, ideal for surgical use in reconstruction of the bladder or urethra.

concept grant, the aim is to see whether PABM could act as a support for the otherwise vulnerable lining, to give it inherent strength and protection, while retaining the necessary flexibility.

A proof of concept animal study, funded by the Medical Technologies IKC, found that PABM enabled better tissue regrowth after urethra surgery compared to an alternative biomaterial which has already been tested in clinical use. The team, from the University of York and Leeds Teaching Hospitals Trust, assessed cellular infiltration of the biomaterial using a new method of quantitative analysis, to give the industry partner in the project, Tissue Regenix, a solid evidence base for future commercialisation.

Lead researcher, Professor Jenny Southgate from the University of York, said: “These studies plug the gaps in knowledge so our commercial partner, Tissue Regenix, can properly assess the potential clinical and economic benefits of the material and decide if they will take it forward. Some questions still remain, but we already have further work planned to address these.”

A further animal study is now underway, testing PABM in bladder reconstruction – specifically auto-augmentation, where the muscle wall is removed to allow the bladder’s inner lining to extend. Also funded by an IKC proof of

Part of the project has also involved developing a commercially-scalable method of producing PABM. This technology, developed by a PhD student at the University of Leeds, is now being transferred to Tissue Regenix as they continue to work with academic and clinical colleagues to trial surgical uses for the material.

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Trials of a new tissue engineering scaffold to repair osteochondral defects have shown it enables better regrowth of both bone and cartilage, compared to commercially available scaffolds.

Using a combination of titanium and polymer matrix, the new scaffold mimics the structure of the cartilage and underlying bone. Results from the first large animal trial of the technology showed that, in just three months, the titanium matrix of the scaffold had supported new bone growth with strong mechanical properties. This ensured good support for the overlying cartilage layer, leading to improved cartilage regrowth into the polymer matrix.

The aim is that the scaffold could provide a one-step surgical treatment for large osteochondral defects, enabling a faster and cheaper alternative to joint replacement to improve the quality of life for a larger number of patients with osteoarthritis.

The technology, developed by a team at UCL (University College London) with proof of concept funding from the IKC and Arthritis Research UK, has already had its moment of fame on the Channel 4 TV series The Supervet. Star of the show, Professor Noel Fitzpatrick, used it to successfully treat

“OUR SCAFFOLD HAS THE STRENGTH NEEDED TO BEAR THE PHYSICAL LOAD OF THE JOINTS AND ITS PATENTED BIOMEDICAL STRUCTURE ENCOURAGES CONSISTENT CARTILAGE FILL. THIS MEANS IT HAS THE NECESSARY PROPERTIES TO MEET THE GROWING NEED FOR CLINICAL INTERVENTIONS IN OSTEOARTHRITIS.”

“CHANGES IN ARTICULAR CARTILAGE AS WE AGE CAN LEAD TO OSTEOARTHRITIS, NOW ONE OF THE MOST COMMON CAUSES OF PAIN AND DISABILITY IN MIDDLEAGED AND ELDERLY PEOPLE. THIS KIND OF SCAFFOLD WOULD ENABLE SURGEONS TO INTERVENE EARLIER, TO PREVENT THE DEVELOPMENT AND PROGRESSION OF THE CONDITION.”

DR CHAOZONG LIU, UCL

PROFESSOR GORDON BLUNN, UCL

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a large osteochondral defect in the shoulder of a seven-month-old Italian Spinone puppy, with scans showing good cartilage regrowth perfectly matching the curvature of the joint.

Funding from Innovate UK is now enabling the UCL team, together with Oxfordbased bioengineering company MEStar Ltd and colleagues in China, to prepare the technology for clinical trials and commercialisation, including creating GMP protocols for its manufacture.

“THE HOLY GRAIL OF REGENERATIVE MEDICINE IS THE PERFECT MARRIAGE OF BIOMECHANICS AND BIOLOGY: CELLS MEETING MAN-MADE STRUCTURES SO THAT THEY’RE CUSTOM-SPECIFIC FOR EACH INDIVIDUAL PATIENT. THAT WILL CHANGE MEDICINE FOREVER.” PROFESSOR NOEL FITZPATRICK, (ON THE SUPERVET PROGRAMME FEATURING THE SCAFFOLD)

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INNOVATION & GROWTH

A collaborative approach to translational research is the foundation of a successful partnership between the IKC and Arthritis Research UK.

Translation

through collaboration This year, five new projects have been awarded proof of concept funding and project support.

They include:

An investigation into the use of 3D printing to produce patient-specific knee implants that will avoid the need for total knee replacement surgery.

Professor Richie Gill, University of Bath

Development of a test to identify hip abnormalities in babies. Detecting and treating hip dysplasia in newborns can help prevent early onset osteoarthritis in adults.

Daniel Perry, University of Liverpool

IKC Technology Innovation Manager, Dr Graeme Howling, and Arthritis Research UK’s Research Translation Manager, Dr Sarah Odoi, reflect on the complementary skills of the two organisations that have made this such a successful research translation partnership.

Development of a new regenerative medicine based treatment for degenerative disc disease.

Professor Chris Sammon, Sheffield Hallam University

A pre-clinical investigation of a novel construct for the treatment of joint damage.

Dr Virginie Sottile, University of Nottingham.

partnerships with other organisations, again based around proof of concept funding calls.

We hope to be announcing a further POC funding call with Arthritis Research UK later this year.”

SARAH ODOI: “Some of the most

learned from working with Arthritis Research UK is how to involve patients and the public in our work. Through Arthritis Research UK’s strong links with patients, each of our proof of concept projects now has strong patient participation to help advise from an end user point of view – this is an approach that we want to develop for other IKC programmes.

interesting and valuable aspects of working with the IKC have been seeing how they manage the translational research process and the expertise they draw together to review projects. We’ve learned some useful lessons about how to evaluate these kinds of technologies. Their networks and links with industry have also added an extra layer of credibility to our growing capability in research translation.

“The model we’ve developed together has worked so well that we’re planning similar

“I think the IKC approach is really productive, in terms of encouraging more academics

GRAEME HOWLING: “What we’ve really

DR GRAEME HOWLING AND DR SARAH ODOI

Development of a standard computerised approach that can reliably detect and analyse spinal fractures in patients with osteoporosis.

Professor Alejandro Frangi, University of Sheffield

into this field and identifying and supporting promising early stage projects, so they’re in a position to apply for proof of concept funds – though of course, there’s always more work to be done. I particularly like the way that the IKC encourages researchers to think broadly about their projects and set realistic expectations.

“The IKC process also helps researchers understand that progressing a technology for the benefit of patients requires working in a multidisciplinary environment, collaborating with stakeholders that they might not have considered before and in partnership with other organisations. The IKC with Arthritis Research UK can assist in bringing these stakeholders together, and in turn, develop stronger propositions.”

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A licensing deal has been agreed to develop commercial routes for a cleverly-designed brush that can remove stem cells from the synovium and put them to use in repairing damaged knee cartilage.

Arthroscopic brush can promote

stem cell healing Knee cartilage repairs are commonly treated using microfracture surgery, in which small holes are drilled into the bone near the damage with the aim of releasing bone marrow stem cells. A blood clot, formed during the drilling, holds these stem cells at the injury site where they can carry out repairs.

Using the arthroscopic brush technique, synovial stem cells are also released into the blood clot, providing additional healing capabilities.

The synovium contains a far higher concentration of stem cells than bone marrow, and their regenerative potential in laboratory studies has proved extremely promising.

Significantly, surgeons should also be able to use the brush with only minor changes to their surgical practice.

The licensing agreement, with Leeds-based medical device company, Xiros, paves the way for the device to be manufactured and marketed to surgeons.

THE RESEARCHER’S PERSPECTIVE “Working with the IKC, I was able to get sound advice on how to apply for proof of concept funding to take the research forward and the IKC team have stayed in close contact since that point. They were responsible for introducing us to Xiros and they’ve also helped guide us through the project to get us in a position for our clinical trial and commercial licence.

“We’ve worked with clinicians at Chapel Allerton Hospital and with the IKC to refine the design of the brush to make it as easy to use and as effective as possible. These cell populations were discovered through Professor Dennis McGonagle’s work in the Faculty of Medicine and Health at Leeds, but their existence is still not widely recognised, so quite a big part of the project has also been to educate surgeons and industry about the potential of synovial stem cells.

“Having been introduced to research translation, I’m very keen to find out more. I’ve been able to do a secondment with the IKC, helping evaluate new proposals and contributing to the Science and Innovation Audit, a Government-sponsored audit of medical technology capabilities in the Leeds City Region.”

Dr Thomas Baboolal, Faculty of Medicine and Health, University of Leeds

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INNOVATION & GROWTH

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THE CLINICIAN’S PERSPECTIVE “The great thing about this project was that we were able to get involved right at the start, to help guide the design process and work alongside the researchers and the IKC. The real key was close communication and lots of collaborative working – that enabled us to identify and iron out any flaws straight away.

“The initial results from the proof of concept work are very promising – the stem cells liberated from the synovium are forming cartilage in the lab. The next step is to get clinical proof of that, and we’ve just started a small scale clinical trial of 20 patients.

“One of the reasons this technology is going to be attractive to clinicians and to the NHS is it’s a low-cost option. It requires no specialist equipment beyond the brush itself. If the clinical trial is successful, this could bring a cheap revolution to heal cartilage defects in the knee – and possibly other joints as well.”

Owen Wall, Consultant Orthopaedic Surgeon, Chapel Allerton Hospital, Leeds

THE PERSPECTIVE FROM INDUSTRY “Once the clinical trial data is available, we will be able to demonstrate clearly to surgeons the usefulness of this device and, at that point, we can start to put in place processes to produce the brushes and develop commercial routes.

“Xiros specialises in commercialising implants and fixation devices, many of which are implanted arthroscopically. Positive results from the clinical trial would give us cause for optimism about the commercial potential of this technology. The brush will be one additional step that surgeons could include very easily within a couple of minutes at the end of surgery. If we can show the benefits clearly, we expect surgeons will be enthusiastic about adopting it.”

Dr Bahaa Seedhom, Chairman, Xiros DR THOMAS BABOOLAL FACULTY OF MEDICINE AND HEALTH, UNIVERSITY OF LEEDS

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SO MANY PEOPLE GO TO CLINICS AND TO A&E DEPARTMENTS WITH CHEST PAINS WHO DON’T ACTUALLY HAVE A CARDIAC CONDITION AT ALL...

THAT PUTS A MASSIVE BURDEN ON HOSPITALS AND PATIENTS.

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INNOVATION & GROWTH

New heart scanner offers detailed, rapid assessment Technology that can detect subtle changes in the heart’s electromagnetic signals could enable physicians to carry out a rapid and sophisticated We assessment of a patient’s cardiac health – enabling healthy patients to be sent home without costly and time-consuming referrals.

Magnetocardiography, the technology that promises this breakthrough, has been in existence for about 50 years, but because of the size of the machines and their cost, they have not yet been adopted in the clinic.

Leeds physicist Professor Ben Varcoe approached the IKC for assistance to develop a new, smaller version of the scanner that he believed could offer a genuine alternative to traditional electrocardiograms and cardiac biomarker testing.

“After we approached the IKC they did two go through a full range of tests, and that puts things that were absolutely pivotal,” recalls a massive burden on hospitals and patients.

Professor Varcoe. “They put a project manager I wanted to find a way that we could address asked thetoexperts developing this project this what contributed to get itsa success. in place guide the development process, problem.

With MCG, we much finerincluding helping us to negotiate the processes grained look at what’s going on, so we’re able of protecting intellectual property and navigate to identify with confidence those patients who through the regulatory pathways. They also don’t have anything wrong with their heart and provided proof of concept funding. From then avoid sending them for further evaluation.” on, our aim was to develop our technology to the point where it was investable.”

Existing magnetocardiography machines are huge and unwieldy because they have to Magnetocardiography (MCG) measures the insulate against background noise. Professor electromagnetic fluctuations of the heart, Varcoe’s team used quantum engineering rather than measuring the voltage produced. to remove the background noise and enable This gives a much more detailed picture the technology to shrink. They also worked to than is possible with an ECG. That means a optimise the sensors, creating a machine that greater range of symptoms can be identified was accurate, portable and affordable. and patients exhibiting none of these can be sent home. According to Professor Varcoe’s With the IKC funding, the team was able to estimate, up to £200m per year could be saved carry out a small scale clinical trial, before by avoiding unnecessary hospital referrals. spinning out a company, Creavo Medical Technologies, and looking for investment. The “The idea for this technology came from my device, now called Vitalscan, is being designed own experience of attending a cardiology specifically for use in A&E departments, where clinic,” says Professor Varcoe. “I had to wait a trained nurse would be able to carry out a five hours and when I finally got to see a scan in around ten minutes. cardiologist, he said: ‘Oh, finally – somebody with a problem’.

A 750-patient trial is underway at four hospitals in Sheffield, Leicester, Bristol and Nottingham, “So many people go to clinics and to A&E with a further multi-centre trial planned in departments with chest pains who don’t actually the US. If successful, the company will start have a cardiac condition at all, but still need to marketing the device towards the end of 2018.

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Regen. Magazine 2017

Innovative partnerships

to tackle unmet

clinical need Building on translational expertise developed within IKC and Regener8, the Translate programme is developing nationally-leading capability in medical technology innovation in the Leeds City Region.

Funded by the HEFCE Catalyst Fund, Translate is bringing together world-class expertise from the Universities of Leeds, Bradford, Huddersfield, Leeds Beckett and York to establish a sustainable community of academic, industry and clinical partners that are committed to working in partnership to deliver a strong local economy and patient benefits.

ASSISTIVE TECHNOLOGY More than a million people in the UK are expected to be living with some form of dementia by 2025. Assistive technologies are crucial to tackling this growing challenge, to address complex issues in independence and care.

MEDICAL TECHNOLOGIES FOR REHABILITATION Translate has joined forces with the Healthcare Technology Co-operative, Devices for Dignity, to find new ways to improve the lives of patients with chronic health conditions.

Leeds City Region universities have extensive expertise in dementia care and support and in developing assistive technologies. The Translate programme decided to bring these two specialities together with local healthcare and social services professionals in a workshop to address unmet clinical needs.

Devices for Dignity (D4D) is funded by the National Institute for Healthcare Research (NIHR). Its remit is to work closely with patient groups to identify and develop interventions that can help tackle issues such as loss of independence or dignity among patients with long-term conditions.

As well as delivering a targeted innovation development programme to enhance innovation awareness, understanding and capacity among Leeds City Region academics, Translate’s dedicated team of Technology Innovation Managers work in partnership to accelerate the successful translation of medical technology ideas and academic research projects towards commercialisation.

Key to making the workshop a success was the partnership with ALLINN (Assisted Living Leeds Innovation Lab). Set up by Leeds Beckett University and Leeds City Council, ALLINN offers end user consultation services to companies developing assisted living technologies. It was ideally placed to support Translate in bringing together relevant care and support organisations to identify key areas of need in this rapidly growing area.

In partnering with Translate, D4D is able to bring clinical insight and expertise to help design projects alongside Translate’s community of researchers. Through their wider network, Translate is also able to involve existing partners from other research institutions and industry across the UK.

Partnering with key national organisations, Translate is developing and delivering a series of innovation workshops that bring together academics, clinicians and industry to co-develop solutions to validated unmet clinical needs. With the support of Translate’s Technology Innovation Managers, these ideas are now coalescing into distinctive projects and funding proposals.

Within one month of the workshop, researchers at Leeds Beckett University and the University of York began working with Translate to turn one of the ideas from the day into a grant proposal for a new collaborative pilot project. This was submitted to the Big Lottery Fund Disabled Research and Independent Living and Learning (DRILL) programme at the end of July 2016.

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Initial project ideas were discussed at an innovation workshop and D4D is now working closely with Translate to develop these into detailed proposals.

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COMMUNITY

Community A steadily growing community in the field of regenerative devices has been a cornerstone of Regener8’s success.

Now, through extensive networking and partnership-building, the IKC and Regener8 partnership is continually extending its reach and influence to support this fast-expanding sector.

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Regen. Magazine 2017

Rules of THE REGENER8 NETWORK

BUILDING CONNECTIVITY

As a stakeholder group, Regener8 has established excellent links regionally and nationally, enabling IKC and Regener8 to harness expertise from throughout the N8 group of universities and from a much wider network of academic, industry and clinical contacts.

Equally valuable are the links with organisations such as the Knowledge Transfer Network, Innovate UK, Medilink and the Academic Health Science Networks.

The strategic alliance forged between the IKC and Regener8 is also supporting and strengthening links with sister programmes such as MeDe Innovation, where skills and expertise are closely shared.

Professor Mike Raxworthy, Regener8’s Operations Director, explains: “Through Regener8, we’re now reaching even further afield, forging national and international partnerships with industry. In terms of our university membership, we now talk about ‘N8 Plus’, which includes, amongst others, major regional institutions such as the Universities of Bradford, Hull, Salford and Huddersfield.”

PROFESSOR MIKE RAXWORTHY OPERATIONS DIRECTOR, REGENER8

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A quarterly newsletter issued by Regener8 draws partners and stakeholders together, with news and events, but also insights into recent developments, new technologies, and funding opportunities of direct relevance to the regenerative devices community across the UK.

“Our expertise in delivering skills development training has enabled us to work closely with Leeds’ Centre for Doctoral Training in Tissue Engineering and Regenerative Medicine, where we worked in partnership with the Royal Academy of Engineering to deliver the MedTech BEST programme,” says Professor Raxworthy. (see page 30) “In addition, the models of strategic partnership we have developed with organisations such as Arthritis Research UK continue to be developed and adapted as we also look to forge new alliances with other organisations working within the medical devices and regenerative medicine sectors.”

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COMMUNITY

THE STRATEGIC ALLIANCE FORGED BETWEEN THE IKC AND REGENER8 IS ALSO SUPPORTING AND STRENGTHENING LINKS WITH SISTER PROGRAMMES SUCH AS MEDE INNOVATION, WHERE SKILLS AND EXPERTISE ARE CLOSELY SHARED. EXTENDING THE WORKSHOP MODEL The series of workshops organised during the year by the Translate programme has provided the opportunity for Regener8 to involve participants from the N8 Plus region to complement those from the Leeds City Region invited by Translate.

on the engagement process successfully developed through the Translate programme. What’s particularly exciting about these events is that we’re seeing a convergence of technologies from many different fields being brought together to address distinctive challenges.”

This has proved to be a successful and popular model for identifying and developing new projects and collaborations. Opportunities to meet people face-to-face remain vital for establishing new partnerships and connections. IKC and Regener8 are planning further workshops, building on the Translate approach, but with a focus on developing an improved understanding of clinical challenges in order to frame early-stage projects which could attract further funding. These will be rolled out through Regener8 to a wider group of universities and industry partners.

“We have plans to arrange workshop events to assess needs and design projects in areas such as surgical robotics and imaging and diagnostics in non-hospital settings,” explains Professor Raxworthy. “These will be modelled

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Regen. Magazine 2017

Widening markets, extending reach, growing capability The IKC Regener8 Conference is a key event in the regenerative medicine community calendar. With more than 150 people joining us to exchange ideas and network, the event is a great opportunity to forge new connections and to keep up to date with recent developments in the sector.

Our theme for this year’s conference is: ‘Widening markets, extending reach, growing capability’. Within this, there’s much to report and share – both in terms of our expanding networks and partnerships, and in terms of the IKC and Regener8’s extended focus, says Rowan Grant, Communications and Engagement Manager for Medical Technologies at Leeds.

Our vision is to see regenerative devices established as a £1bn industry in the UK by 2025. The convergence of technologies is likely to be an important contributor to the reaching of this goal and so we’ve directed our

efforts towards extending the breadth of new technologies that we are helping to develop, and to increasing the number of companies with which we work.

That growth is reflected in the variety of speakers we are welcoming to this year’s conference. Our keynote speaker, Dr Pierre-Alexis Mouthuy, of the University of Oxford’s Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, has done some truly inspiring work in the designing and fabrication of scaffolds and implants for osteochondral defects and tendon repair, while IKC researchers including Dr Caroline Wilcock and Professor Animesh Jha, have plenty to share in terms of their research translation journeys.

We’re also excited to be showcasing some of our technologies that have completed their ‘bench to bedside’ journey, with presentations from industry partners including Tissue Regenix, Xiros and Invibio.

ROWAN GRANT

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Our drive to grow capability across our networks starts with skills development among early career researchers, but keeping up to date with the skills and knowledge required to translate research effectively is a key part

of all our projects. Deborah Morrison, from NICE, and Robin Martin, from Smith & Nephew, will be delivering insights into some of the evidence requirements for new technology adoption and some of the support available.

Finally, no IKC Regener8 Conference would be complete without our proof of concept poster pitches. We’re looking forward to some really innovative entries that will demonstrate the breadth of IKC Regener8 innovation.

Rowan Grant Communications and Engagement Manager, Medical Technologies at Leeds

OUR VISION IS TO SEE REGENERATIVE DEVICES ESTABLISHED AS A £1BN INDUSTRY IN THE UK BY 2025.

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COMMUNITY

Community

tweets

The medtech community is increasingly active on Twitter – why not join the conversation?

Lise Sproson@LiseSproson

“Great ideas exchange at Innovation workshop.” @Devices4Dignity @regener8network @TranslateMedTec Danielle Miles@Dr_D_Miles

“Idea generation is well underway at the wound characterisation & treatment workshop.” @TranslateMedTec @medtechleeds

N8 Research@N8research

John Fisher: the UK is the most efficient at producing science outputs per dollar spent globally.

Ortheia@Ortheia @TranslateMedTec

is a powerful city-wide programme in #LeedsCity Region to make impact in #REF2021 a success. @Ortheia proud to be part of it.

James Lapworth@JWLapworth

Prof John Fisher, @MeDe_ Innovation, summarising interim findings from BEIS #MEDTECH Science & Innovation Audit.

Health Tech Alliance@HTA_Tweets audit for @beisgovuk to identify

Marcus Orton@MarcusOrton

Looking for inspiration at MedTech BEST Final Pitch with Medical Technologies IKC / University of Leeds.

clear constraints from #medtech sector bringing products to market. #MTIEXPO

Duncan Wood@duncanwood Great start to the #MTIExpo

this morning, just kicked Interesting to work with off the conference with one #academics and #clinicians to of two CBEs I have met generate #innovative ideas in this morning, John Fisher, wound characterisation and impressive line up! treatment.

MEDNET@MednetHealth

Mike Raxworthy@Mikerax

Annual Conference in #Leeds finally here. Looking forward to a good day.

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Regen. Magazine 2017

Supplying new skills to a growing industry

Through skills development programmes such as MedTech BEST (Business and Entrepreneurial Skills Training), delivered in partnership with the Royal Academy of Engineering, IKC Regener8 can help early career researchers explore different career options. At the same time, we are helping ensure their valuable skills are retained by the medical technology sector.

“The MedTech BEST competition offered me and my team the opportunity to test the water in the sink-or-swim world of medical device start-ups. We practised every employability skill in any ‘top ten’ list you can find. Here’s what I learned:

Making a career move from academia to industry can seem like a giant leap. IKC Regener8 offers support and advice to researchers interested in taking the first step.

“Commercial awareness is routinely cited as one of the most important skills for graduates. Bringing our hypothetical product to market involved far more than identifying an unmet need and plugging the hole. Understanding the market, identifying stakeholders and planning how the product could reach them were all vital. The investment pitch finale of the competition highlighted the importance of financial viability. If the numbers don’t add up, it won’t work anyway – even if you do manage to get investment.

“Planning and organisation is another skill always included in the top ten and mapping the future path of a product is key. This gives direction and purpose and shows investors that you know where you want to be. The map may change often, but there is always a map to refer to.

“At the finale, one of the judge’s criticisms was that our team lacked the broader range of skills and experience to sustain the business. Identifying weaknesses and effectively addressing them is critical. During MedTech BEST I’ve realised I need to trust my teammates, identify people’s strengths and delegate for efficient teamwork.”

Ben Golland PhD Student, CDT in Tissue Engineering and Regenerative Medicine Institute of Medical and Biological Engineering, University of Leeds 30

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“MedTech BEST pushed us to explore the realities of business and innovation and apply that knowledge to medical devices. It was important to first understand the industry, and this was aided by presentations given by real-world scientists, CEOs, investors and regulators.

“All these experts provided anecdotal evidence of the struggles and achievements gained in this industry, as well as providing the knowledge we required to support our business. For me, the development of this awareness was by far the most rewarding, as it provided a chance to network and learn with experienced individuals in the field.

“My leadership, organisational and team-working skills were improved whilst participating in MedTech BEST, and my presentation and communication skills were tested during the pitch and the creation of a business plan and investment memo.

“Not only do I believe that this programme has improved my employability skills, but I believe it has opened up new career options for the future that I may have not considered prior to taking part.”

Lekha Koria PhD Student, CDT in Tissue Engineering and Regenerative Medicine, Institute of Medical and Biological Engineering, University of Leeds

“I was involved with the IKC’s Career Architect programme in 2013 when I wanted to explore what other options were available for a post-doctoral researcher apart from a career in academia.

“Since beginning the CDT in Tissue Engineering and Regenerative Medicine course at the University of Leeds, I have been continually encouraged to develop my personal and employability skills.

“The programme was managed excellently by career strategist, Ruth Winden and researcher training officer, Patricia Gray. They really helped broaden my understanding of what else is out there and just how many transferable skills doing a PhD and being a researcher gives you; including problem solving, initiative and enterprise, planning and organising, as well as project and self-management.

“As well as attending two innovation-based modules at Leeds University Business School, I attended monthly Innovation Seminars which ranged in topics from ‘Regulatory Routes for Medical Devices’ to ‘Healthcare Economics’. These helped me understand the pathway to commercialisation for medical devices and the necessary time, funding and business knowledge required alongside scientific research.

“The programme had a great peer coaching system and plenty of opportunity for help and feedback. The careers coaching I received, from interview practice to assistance with CV writing, was a huge help in getting the position that I have today.

“My CASE-funded PhD project based on developing an antimicrobial scaffold for soft tissue repair is sponsored by Neotherix Ltd in York.

The CEO, Professor Mike Raxworthy, is an active member of my supervisory team and provides an important industry focus to my supervision meetings.

“I was given the opportunity to work on a secondment for the IKC in Medical Technologies at Leeds, which enabled me to get the job-specific experience I needed to be in my current role. I have also kept in touch with one of the careers coaches from the Careers Architect programme who has been extremely helpful in helping me understand and demonstrate what employability skills I have!”

“I have attended business meetings with the company to look into the proof of concept research and patent background of the product I’m researching. I feel that this experience of working on a real-world application will prove invaluable when applying for jobs on completion of my PhD and in my future career.”

Dr Andrew Aldridge

Amy Smith

Technology Innovation and IP Development Manager Medical Technologies IKC

PhD Student, CDT in Tissue Engineering and Regenerative Medicine, Institute of Medical and Biological Engineering, University of Leeds 31

The regenerative devices community magazine

issue 08 2017

med-tech@leeds.ac.uk

The regenerative devices community magazine

Taking on the giants Rules of engagement Injectable paste tackles deep bone infection

issue 08 2017

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