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
The porous, ‘sponge’-type molecules have an enormous internal surface area
This allows their use as ‘molecular flasks’ or ‘molecular containers’ that change the reactivity and properties of encapsulated molecules
Scientists from Trinity College Dublin and AMBER, the Science Foundation Ireland-funded materials science research centre hosted in Trinity College Dublin, have created ‘molecular cages’ that can maximise the efficiency of converting molecules in chemical reactions, and that may in future also be used as sensors and drug-delivery agents. The cages can be packed with different molecules, many of which have a specific task or functionality. Incredibly, a teaspoon of powder containing these cages provides a greater internal surface area to boost reactivity and storage capacity than would be provided by an entire football field (4000 m2/g).
This enormous intrinsic surface area relative to the weight of the structure in combination with the solubility offers great promise for energy conversion, while the structure blueprint (hollow, with sub-cages) allows different molecules to be discretely contained within. This latter feature is key in increasing the potential uses for these ‘metal-organic-organic polyhedra’ (MOP), because it means materials can be packed so as to react only when specific conditions present themselves.
One such example is in bio-sensing and drug-delivery, with a biological cue required to kick-start a chemical reaction. For example, a drug could be encapsulated in one of these MOP in the knowledge that it would only be released at the specific target site, where a specific biological molecule would trigger its release.
The researchers behind the breakthrough, which has just been published in leading international journal Nature Communications, also hope to develop light-active porous, metal-organic materials for use in green energy. The dream would be to create a molecule that could simply use light to convert energy – essentially replicating the way plants produce energy via photosynthesis.
Professor in the School of Chemistry at Trinity College Dublin, and Investigator in AMBER, Wolfgang Schmitt, led the research. He said: “We have essentially created a molecular ‘flask’ or better ‘sponge’ that can hold different molecules until a specific set of conditions spark them into life.”
“Hollow cage-type molecular structures have attracted a lot of scientific attention because of these features, but as the number of potential applications has grown and the target systems and environments become more complex, progress has been hampered by the lack of structures with sufficiently large inner cavities and surface areas.”
“The MOP we have just created is among the largest ever made, comprising a number of internal sub-cages, providing numerous different binding sites. The nano-sized compartments can potentially change the reactivity and properties of molecules that are encapsulated within the confined inner spaces and, as such, these cages can be used to promote distinct chemical reactions. Thus, these molecules have the potential to mimic biological enzymes.”
The journal article describes the structure of the new cage molecule, which is composed of 36 copper atoms and is made up of 96 individual components. The article can be read at Nature Communications.
A new collaboration between researchers at RCSI (Royal College of Surgeons in Ireland), and Trinity College Dublin (TCD) as part of the AMBER, SFI funded materials science centre in conjunction with Integra LifeSciences, a world leader in medical technology, aims to develop, and bring to the market, a new product to facilitate the repair of large nerve defects in the body. This €1.4 million research programme will run for three years.
This project is led by Prof Fergal O’Brien (Dept. of Anatomy, RCSI & Deputy Director in AMBER) in partnership with Prof Conor Buckley from the Trinity Centre for Bioengineering (TCD).
Peripheral nerves link the brain and spinal cord to the other parts of the body, such as the muscles and skin. They can be damaged through disease, trauma and burns resulting in interference with the brain’s ability to communicate with tissues resulting in the loss of motor or sensory function to muscles and skin. This can have significant deterioration in a patient’s quality of life.
Peripheral nerve injury is a major clinical problem and is known to affect more than 5 million people worldwide every year. It is estimated that five percent of multiple trauma patients have peripheral nerve injuries. Prompt surgical intervention is needed but if the injury size is larger than five millimetres, the primary treatment option available in most cases is by autograft which involves removal of nerve tissue from another part of the patient’s body and transplantation to the site of injury. Unfortunately, autografts are hampered by a number of issues including the limited availability of donor tissue and often functional recovery for patients can be poor. As a result the RCSI & TCD team in AMBER are working with Integra LifeSciences to develop a next generation nerve graft capable of repairing large nerve defects without the need for invasive secondary surgeries.
RCSI’s collaboration with Integra began in 2005 and has deepened in the intervening years through the AMBER Centre. This current project marks the second engagement in the area of peripheral nerve repair between the parties. The first project was successfully completed at the end of 2016 and resulted in a patent being filed on technology generated under the project. This current engagement builds on this research.
Dr. Simon Archibald, Vice President and Chief Scientist from Integra LifeSciences said, “The demand for nerve repair biomaterials is increasing due to the aging population and rising number of nerve injuries and nerve surgeries. Our aim is to treat largescale nerve defects in the body and introduce this new technology to our portfolio of existing nerve repair products.”
Professor Fergal O’Brien, Professor of Bioengineering & Regenerative Medicine & Deputy Director of AMBER said “Building on a wealth of expertise in biomaterials development from the Tissue Engineering Research Group at RCSI, our hope is to work with Integra to see this new technology translate to the benefit of patients and society.”