Dr Cathal Kearney from RCSI (Royal College of Surgeons in Ireland) Department of Anatomy and the Science Foundation Ireland funded AMBER (Advanced Materials and BioEngineering Research) centre has been awarded a €1.375 million European Research Council’s (ERC) Starter Grant for ground-breaking research to combat diabetic foot ulcers. The highly prestigious grant supports researchers across Europe to set-up their own research teams and pursue potentially life-changing innovations. In total, 406 grants were awarded this year to projects across Europe with Dr Kearney receiving one of just two given to Irish institutions.
People with diabetes across the world are at risk of diabetic foot ulcers with up to a quarter of the 422 million diabetic population expected to suffer from the ailment in their lifetime. These wounds are very difficult to heal and are often prone to infection which can lead to amputation. It is estimated that every 30 seconds a limb is amputated as a result of a diabetic foot ulcer. In Ireland alone, 2,400 people were hospitalised in 2015 with the condition and 451 of these cases resulted in amputations.
Dr Cathal Kearney, Principal Investigator in the Tissue Engineering Research Group, RCSI received the funding for his research titled ‘BONDS: Bilayered ON-Demand Scaffolds for diabetic foot ulcers’. The goal of this research programme is to develop a new technology-driven device that will support the body’s own cells to grow new tissues to repair skin damage on the foot caused by ulcers. The device will be made of a sponge-like material and DNA will be delivered inside the device using a novel technology. The delivered DNA will then direct cells that enter the device to heal the wound.
Speaking about the funding, Dr Kearney said: “I am honoured to have been awarded this prestigious research grant from the ERC. In Ireland, it is estimated that €70 million/year is spent on the treatment of diabetic foot ulcers, with almost one in five cases resulting in amputation. This research has the potential to change that for the better for people with diabetes not only in Ireland but across the world.”
Director of Research and Innovation at RCSI, Professor Ray Stallings, welcomed the announcement saying: “This award to Dr Kearney is a testament to his stellar research in the area of biomaterials, and the expertise of RCSI’s Tissue Engineering Research Group that is addressing health issues arising from a range of chronic conditions such as diabetes. This innovation could transform the lives of diabetes patients across the world, and we look forward to seeing the outcomes of Dr Kearney’s work as his research expands as a result of this important grant.”
Dr Kearney has previously secured the prestigious Fullbright scholarship to attend MIT and Harvard University and the Marie Sklowdowska-Curie Fellowship at RCSI. His innovative work on drug delivery has been published in a number of high impact journals. Dr Kearney combines his research interests with a passion for teaching, having won the RCSI President’s Teaching Award 2017.
These coveted ERC Starter Grants support research in the life sciences, physical sciences and engineering, and social sciences and humanities and form part of the “Excellent Science” pillar of the European Union research and innovation programme, Horizon 2020.
Carlos Moedas, European Commissioner for Research, Science and Innovation, said: “Top talent needs good conditions at the right time to thrive. The EU provides the best possible conditions at the early stages of a researcher’s career through the ERC Starting Grants. That’s why this funding is so crucial for the future of Europe as a science hub: it keeps and attracts young talent. This time the ERC attracted researchers of 48 different nationalities based in 23 European countries. It’s an investment that will pay off, boosting the EU’s growth and innovation.”
Craniosynostosis is a developmental condition where children present premature fusion of the skull sutures. This condition affects one out of 2500 live births and can cause damage by limiting brain growth. Scientists based in Ireland are investigating the mechanisms that speed up bone formation in children diagnosed with craniosynostosis. This follows the identification of local microenvironmental changes as a key player in the abnormal activation of a series of genes involved in the accelerated bone formation in the prematurely fused sutures.
Clinicians at the National Paediatric Craniofacial Centre at Temple Street Children’s University Hospital, together with scientists at RCSI (Royal College of Surgeons in Ireland) and the Science Foundation Ireland funded AMBER (Advanced Materials and BioEngineering Research) centre, compared the behaviour of cells from prematurely fused sutures and cells from unfused sutures in order to understand how changes in the local physical environment of the skull directs the premature suture fusion.
Their study, published in Scientific Reports –a leading open access journal from the publishers of Nature - identified that cells from fused sutures have a greater sensitivity to changes in their local environment while also discerned the genetic mechanisms that control that behaviour. In particular, cells from fused sutures prematurely commit towards a bone forming cell type. These insights in the mechanisms by which changes in the physical environment promote the premature fusion of the skull sutures may provide the opportunity to develop new therapeutic strategies for bone repair.
Mr. Dylan Murray, Lead clinician at the National Paediatric Craniofacial Centre at Temple Street Children’s University Hospital commented, ‘This study was possible with the consent of the parents of the children we operate on in Temple Street who have the condition craniosynostosis. Whilst it will never be the case that a fused suture can be treated with medications to reopen them, there are many applications of this scientific breakthrough. An example of this is the possibility of impregnating bone scaffolds with these genes. This will help to stimulate new bone formation. This can be used instead of bone grafts.
Professor Fergal O’Brien, Head of the Tissue Engineering Research Group in RCSI, Deputy Director of AMBER and lead PI on the project noted ‘This is a great example of interdisciplinary research between clinicians and scientists. We are particularly grateful to the patients in Temple St and their families who supported this project’
Commenting on the significance of the research, Dr. Arlyng Gonzalez Vazquez, whom together with Dr. Sara Barreto are the joint-first authors on the study, said: ‘Our findings not only shed new light to understand the mechanisms that control the premature fusion of the skull suture in children with craniosynostosis but also provide new targets that can be incorporated into novel therapeutic target-specific biomaterials to enhance bone formation in patients suffering from severe fractures and bone degeneration’.
This work was supported by the Temple Street, Children’s Fund for Health, the Health Research Board, and the Irish Research Council.
RCSI is ranked in the top 250 institutions worldwide in the Times Higher Education World University Rankings (2017-2018). It is an international not-for-profit health sciences institution, with its headquarters in Dublin, focused on education and research to drive improvements in human health worldwide.
Prof. Daniel Kelly, Investigator at AMBER and Director of the Trinity Centre for Bioengineering has been announced as a recipient of the European Research Council’s (ERC) Proof of Concept Grants. This is the 3rd ERC grant awarded to Prof Kelly and the 12th ERC awarded to researchers in AMBER, the Science Foundation Ireland funded materials science centre based in Trinity College Dublin, since its launch in 2013. This funding will provide Prof. Daniel Kelly with €150,000 over 1.5 years and enable him to verify the innovation potential of ideas arising from his existing ERC funded projects, which focus on a novel implant for treating cartilage damage.
Prof. Kelly won the funding for his project entitled ‘ANCHOR’. The aim of ‘ANCHOR’ is to develop and commercialise a new medicinal product for cartilage regeneration. Cartilage damage is a relatively common type of injury, with the majority of cases involving the knee joint. Damage can occur due to injury or wear and tear, and if not satisfactorily treated can lead to osteoarthritis (OA). OA represents a significant economic burden to patients and society in the world, estimates are that 9.6% of men and 18.0% of women, aged over 60 years, have symptomatic osteoarthritis, with 80% of those having limitations in movement and 25% saying they cannot perform their major daily activities of life*. There is currently no cure and in the most serious cases, the entire joint may need to be replaced with an artificial joint, such as a knee replacement prosthesis.
Prof Kelly’s proposed product comprises a cartilage derived 3D scaffold which acts as a template to guide the growth of new tissue by recruiting endogenous bone marrow derived stem cells. What is unique about the therapy is that the scaffolds will be supported by an array of 3D printed biodegradable polymer posts that will anchor the implants into the bone underneath the cartilage. If successful, such an implant would form the basis of a truly transformative therapy for treating degenerative joint diseases like arthritis. The funding will also allow Prof. Kelly to employ a post-doctoral researcher.
Prof. Daniel Kelly, Principal Investigator at AMBER, said “At present the treatment options for OA are limited to surgical replacement of the diseased joint, with a prosthesis. Joint replacement prosthesis also have a finite lifespan, making them unsuitable for the growing population of younger and more active patients requiring treatment for OA. Our 3D printed polymer posts will anchor the implant into the bone and will be porous to stimulate the migration of stem cells from the bone marrow into the body of the scaffold. While various scaffolds like this have been available for some time, they have had limited success, partly because scaffolds need to be anchored securely due to the high forces experienced within the joint. Our 3D printed posts overcome this problem.”
Prof. Michael Morris, Director of AMBER, commented on the announcement, saying “I’d like to congratulate Professor Kelly on successfully securing his 3rd ERC award. He is doing ground-breaking work in his field that will really make a difference to society. This award demonstrates both the excellence and also the quality of the research team that has been built in AMBER.”
Prof Kelly’s project has resulted from outputs and expertise from his previous ERC Starting Grant and his current ERC Consolidator Grant. As part of the ERC Starting Grant STEMREPAIR, he developed a range of porous cartilage derived scaffolds. He is currently developing 3D printing strategies as part of his ERC Consolidator grant JOINTPRINT.
Background on the European Research Council’s (ERC) Proof of Concept Grants
All Principal Investigators in an ERC frontier research project, that is either on going or has ended less than 12 months before 1 January 2017, are eligible to apply for an ERC Proof of Concept Grant. The Principal Investigator must be able to demonstrate the relation between the idea to be taken to proof of concept and the ERC frontier research project (Starting, Consolidator, Advanced or Synergy) in question. Proof of Concept Grants are up to €150 000 for a period of 18 months.
A team of researchers from AMBER, the Science Foundation Ireland funded materials science centre based in Trinity College Dublin, have made a breakthrough in the area of material design – one that challenges the commonly held view on how the fundamental building blocks of matter come together to form materials. Professor John Boland, Principal Investigator in AMBER and Trinity’s School of Chemistry, researcher Dr. Xiaopu Zhang, with Professors Adrian Sutton and David Srolovitz from Imperial College London and University of Pennsylvania, have shown that the granular building blocks in copper can never fit together perfectly, but are rotated causing an unexpected level of misalignment and surface roughness. This behaviour, which was previously undetected, applies to many materials beyond copper and will have important implications for how materials are used and designed in the future. The research was published today in the prestigious journal, Science*. The Intel Corp. Components Research Group also collaborated on the publication.
Electrical, thermal and mechanical properties are controlled by how the grains in a material are connected to each other. Until now, it was thought that grains, which are made up of millions of atoms, simply pack together like blocks on a table top, with small gaps here and there. Professor Boland and his team have shown for the first time that nano-sized grains in copper actually tilt up and down to create ridges and valleys within the material. Nanocrystalline metals such as copper are widely used as electrical contacts and interconnects within integrated circuits. This new understanding at the nanoscale will impact how these materials are designed, ultimately enabling more efficient devices, by reducing resistance to current flow and increasing battery life in hand-held devices.
Professor John Boland, Principal Investigator in AMBER and Trinity’s School of Chemistry, said, “Our research has demonstrated that it is impossible to form perfectly flat nanoscale films of copper and other metals. The boundary between the grains in these materials have always been assumed to be perpendicular to the surface. Our results show that in many instances these boundaries prefer to be at an angle, which forces the grains to rotate, resulting in unavoidable roughening. This surprising result relied on our use of scanning tunnelling microscopy which allowed us to measure for the first time the three-dimensional structure of grain boundaries, including the precise angles between adjacent grains.”
He added, “More importantly, we now have a blueprint for what should happen in a wide range of materials and we are developing strategies to control the level of grain rotation. If successful we will have the capacity to manipulate material properties at an unprecedented level, impacting not only consumer electronics but other areas such as medical implants and diagnostics. This research places Ireland yet again at the forefront of material innovation and design.”
Professor Boland is Dean of Research at Trinity, a fellow of Trinity College and a fellow of the American Association for the Advancement of Science. He was the Laureate of the 11th ACSIN Nanoscience Prize (2011) and was awarded a prestigious ERC Advanced Grant in 2013.
* Zhang X, Han J, Plombon JJ, Sutton AP, Srolovitz DJ, Boland JJ. Nanocrystalline copper films are never flat. Science 28 July 2017