Researchers at AMBER, the SFI Research Centre for Advanced Materials and Bioengineering Research, the Trinity Centre for Biomedical Engineering at Trinity College Dublin have developed a new technology to support bone regeneration. Their work presents a step change over current medical interventions in regenerative medicine and opens the door to new therapies to treat substantial fractures and other diseases.
The team have developed a printable ‘bioink’ that enables bone, and its’ supporting blood vessels, to grow in a controlled way and have tested their technology in laboratory preclinical studies. The team have optimised the bioink so that the important growth factors contributing to the natural process of fracture repair and tissue regeneration can be released inside the body in a controlled way, where, and when, they are most needed.
The great potential and problems facing regenerative medicine
A revolution in healthcare through personalised and regenerative medicine is heralded as a key vehicle by which healthcare systems can achieve better outcomes for patients while also helping achieve financial efficiency across the health system. While great therapeutic advances have been made, problems still exist in maximising the potential for regenerative medicine for patients. One key issue facing clinicians has been the ability to deliver specific cues to the body, at the site of disease, to enable the growth of complex tissues such a bone, which also requires integration of blood vessels and nerves to operate in a normal manner.
Despite the tremendous potential of growth factor delivery as a therapeutic mechanism, the results obtained in larger clinical trials have not always shown the expected benefit to patients, with some studies reporting drastic adverse side-effects*. One potential reason for these complications is that the current best practice is to deliver concentrations of growth factor which greatly exceeds normal concentrations in the body. This method neglects the very sensitive complex role of growth factors in tissue regeneration whereby, as new bone and its associated vessels re-grow, different growth factors, at different concentrations, and at different sites within the damaged tissue are required. A more sensitive, controlled, delivery mechanism that takes into account these requirements is needed to maximise therapeutic outcomes.
Advancing a controlled treatment for bone and tissue regeneration
The team focused their attention on solving the problem of controlled growth factor delivery, so that the correct growth factors could be delivered where, and when, they were needed. The team succeeded in developing an approach using 3D bioprinting techniques and funtionalised bioinks to 3D print constructs that contain patterns of growth factors. This pattern is crucial, as it provides the body the necessary cues to regenerate bone itself over time and at specific sites in the injury. Their research allows for controlled tissue regeneration limiting risk of adverse side effects from current approaches and has been published in the high-profile journal Science Advances
Lead researcher on the project, Dr. Fiona Freeman, Marie Curie Fellow in the Trinity Centre for Biomedical Engineering at Trinity College Dublin and Harvard Medical School says “This study demonstrates the potential of growth factor printing as a point of care therapy for tightly controlled tissue regeneration. This approach overcomes many of the challenges associated with cell-based therapies by providing the body the necessary cues to regenerate itself rather than implant replacement tissue, or flood the body with excessive levels of growth factors to support regeneration”.
Prof. Daniel Kelly, AMBER researcher and Chair of Tissue Engineering at the Trinity Centre for Biomedical Engineering, Trinity College Dublin who over saw the study says “We have demonstrated a potential clinical utility in the regeneration of large bone defects or the increased vascularization of any 3D printed construct. Our Proof-of-Concept studies established the potential of these growth factor loaded bioinks to induce bone regeneration and vascularisation. The benefit of this precise localization of growth factors in both time and space is that it allows for tightly controlled new tissue formation, thereby reducing off-target effects”.
The team envision that this platform technology could be applied to the controlled regeneration of numerous different tissue types. The next stage of this work is to incorporate it with current on-going cartilage regeneration strategies being developed in Prof. Kelly’s lab to develop 3D bioprinted constructs for the repair of osteochondral defects. The study was jointly funded by the European Research Council (ERC) and the Irish Research Council.
* N. E. Epstein, Complications due to the use of BMP/INFUSE in spine surgery: The 608 evidence continues to mount. Surgical neurology international 4, S343-S352 (2013). 609
* L. B. E. Shields et al., Adverse effects associated with high-dose recombinant human bone 610 morphogenetic protein-2 use in anterior cervical spine fusion. Spine 31, 542-547 (2006). 611
* K. Lee, E. A. Silva, D. J. Mooney, Growth factor delivery-based tissue engineering: 612 general approaches and a review of recent developments. J R Soc Interface 8, 153-170 613 (2011).
Researchers at AMBER, the SFI Research Centre for Advanced Materials and Bioengineering Research and the Schools of Engineering and Pharmacy at Trinity College Dublin, have shed new light on the role of exercise on bone growth. Their work has opened the door to potential new therapies for bone diseases such as osteoporosis.
The team discovered that when bone cells (osteocytes) are subjected to physical loading, similar to that experienced during exercise, they produce signals causing human bone marrow stem cells to grow new bone. This mechanism can be functionalised to create new therapeutic approaches to bone diseases which affect millions of people globally.
Bone growth, osteoporosis and exercise
Around 300,000 people in Ireland have osteoporosis and many more may live with the disease undetected. It can be particularly problematic as we get older when bone regeneration becomes slower. One in 4 men and 1 in 2 women over 50 will develop a fracture due to osteoporosis in their lifetime, according to the Irish Osteoporosis Society. The cost of care for these patients is high, as many require hospitalisation and surgery, with an estimated total cost of care of €653 million.
Finding new ways to treat these diseases will have considerable impact on patients and hospitals.While it is well known that exercise – particularly weight bearing/strengthening exercise – supports bone health, in conjunction with other factors, the specific mechano-biological pathway explaining this relationship has remained elusive.
Cellular level insights into the impact of exercise on bone growth
The Trinity team found that when osteocytes are subjected to a physical load mimicking exercise they release nano-sized vesicles that enhance bone marrow stem cell differentiation, and promote bone formation. Key to this study, and the possibility to advance therapeutic approaches based on this mechanism, was the teams’ discovery of the precise role of the vesicles in the process of bone generation.
The vesicles, when generated by osteocytes under physical loading, act as a communication mechanism, carrying information from osteocytes to bone marrow stem cells. The chemicals inside the vesicles tell bone marrow stem cells to turn into cells fundamental to the process of bone generation. This communication mechanism holds great potential to act as a novel, cell‐free, therapy to enhance bone regeneration.
The Trinity team recently published their findings in the high-profile journal Stem Cells Translational Medicine.
Professor David Hoey, AMBER researcher, Trinity’s School of Engineering, said: “This work highlights the importance of considering physical factors in biology and medicine, demonstrating an interesting example of where mechanics alone was sufficient to change cell behaviour, and in this case, support bone growth. This gives us significant insight into the role of exercise in bone formation and specifically intra-cellular communication.
“We identified that mechanically activated vesicles can be harnessed to promote stem cell differentiation in the lab. Harnessing these small vesicles we hope to develop new therapies for bone regeneration that mimic the beneficial effects of exercise on bone, potentially transforming how millions suffering from osteoporosis and bone defects are treated each year. Our next step is to test their efficacy in pre-clinical models.”
Research was conducted in collaboration with Professor Lorraine O’Driscoll from Trinity’s School of Pharmacy. It was funded by the Irish Research Council, the European Research Council and Science Foundation Ireland.
Scientists at AMBER, the SFI Research Centre for Advanced Materials and Bioengineering Research, CRANN and the School of Physics at Trinity College Dublin, have secured investment in a new international collaboration that will focus on reducing atmospheric carbon dioxide and tackle climate change challenges.
The project titled ‘Development of a Highly Efficient and Practical Carbon Management System for Improving Qatar’s Sustainability: A Holistic Approach’, will be lead by Qatar University and Qatar Green Building Council (QGBC), alongside teams from the University of Calgary (Canada), Imperial College London (UK); Georgia State University (USA); and Leibniz Centre for Agricultural Landscape Research (Germany) and Trinity College Dublin.The 5 year project has secured €5.4 million from the Qatar National Research Fund and private co-funding.
The project aims to develop an efficient and practical carbon management system. Using innovative materials, the proposed technology aims at having the capacity to reduce atmospheric carbon dioxide (CO2) concentrations by capturing excess CO2 directly from the atmosphere, and using the captured gasses to feed agricultural greenhouses and also converting it into value-added products.
Prof. Stefano Sanvito, AMBER, Director or CRANN and School of Physics explains, “We aim at developing new technology for controlling and improving air quality, through CO2 capturing and reconversion. The project will have strong impacts in sustainable energy, health and food security. We are thrilled to work with a consortium covering all aspects of the problem, from the most fundamental physical/chemical ones, to the development of efficient air purification systems, to the evaluation of their economic impact. My team will design new metal-organic molecular structures for CO2 capture using a combination of advanced electronic structure theory and machine-learning methods.”
Extending his congratulations to the team, Executive Director of Qatar National Research Fund, Dr Abdul Sattar Al Taie said: “We believe this cluster project will ensure that Qatar benefits from the research outcomes and strengthen mutually beneficial and constructive collaborations between relevant local and international stakeholders.”
Project lead, Dr Marc Vermeersch, executive director of Qatar Environment and Energy Research Institute (QEERI) at Hamad Bin Khalifa University, added: “We are honoured to be leading this project, and I congratulate the team, who showed a lot of effort, resilience and perseverance. This outstanding project will not only contribute to supporting Qatar to tackle its grand challenges in energy, water and the environment, but also build a platform to further enhance collaborations among national stakeholders and promote in-country capacity building through the involvement of graduate students.”
In the early days and weeks of the COVID crisis, there were deep concerns about PPE. Front line workers needed to adjust to the new reality rapidly, adapting to different levels of protection in different clinical situations and scenarios. There was a huge demand on masks.
The most common and most readily available type of mask is a simple paper mask that is secured by elastic loops over the ears. But these have their own problems. Wearing them for long periods of time can cause significant discomfort and chafing around the ears, or at times, the elastic can stretch and the masks became loose. A mask adjuster solves these problems.
As Prof. John M. O’Byrne, Consultant Trauma & Orthopaedic Surgeon, Cappagh National Orthopaedic Hospital, explains: “We realised we needed mask adjusters; a small piece of plastic that loops around the elastic loops in facemasks, are cheap to make, and could be rapidly distributed to front line workers across the country. AMBER technician, Alex Conway, improved on an initial design we provided to him and prototyped the new mask adjusters within AMBER Advanced Research Laboratory with specialist 3D printers. The adjustment Alex made allowed for more variation in the tension of the mask making it more secure, more reliable and more comfortable. We are very grateful to AMBER for their contribution”.
To ensure as many front line workers as possible were given access to the mask adjusters AMBER collaborated with a large supplier to rapidly 3D print and distribute thousands of units nationwide.