Over 130,000 children born in Europe every year will have a congenital anomaly (CA; birth defect). These CAs, which are often rare diseases, are a major cause of infant mortality, childhood morbidity and long-term disability. EUROCAT is an established European network of population-based registries for the epidemiologic surveillance of CAs. EUROlinkCAT will use the EUROCAT infrastructure to support 21 EUROCAT registries in 13 European countries to link their CA data to mortality, hospital discharge, prescription and educational databases. Each registry will send standard aggregate tables and analysis results to a Central Results Repository (CRR) thus respecting data security issues surrounding sensitive data. The CRR will contain standardised summary data and analyses on an estimated 200,000 children with a CA born from 1995 to 2014 up to age 10, enabling hypotheses on their health and education to be investigated at an EU level. This enhanced information will allow optimisation of personalised care and treatment decisions for children with rare CAs. Registries will be supported in using social media platforms to connect with families who live with CAs in their regions. A novel sustainable e-forum, “ConnectEpeople”, will link these families with local, national and international registries and information resources. ConnectEpeople will involve these families in setting research priorities and ensuring a meaningful dissemination of results. Findings will provide evidence to inform national treatment guidelines, such as concerning screening programs, to optimise diagnosis, prevention and treatment for these children and reduce health inequalities in Europe. An economic evaluation of the hospitalisation costs associated with CA will be provided The CRR and associated documentation, including linkage and standardisation procedures and “ConnectEpeople” forum will be available post-EUROlinkCAT thus facilitating future local and EU level analyses.

The European Consortium for Communicating Gene and Cell Therapy Information (EuroGCT) unites 49 partner organisations and institutions across Europe, including the major European advanced therapies learned societies, with the common goal of providing reliable and accessible information related to cell and gene therapy development to European stakeholders. EuroGCT has two major objectives: • To provide patients, people affected by conditions, healthcare professionals and citizens with accurate scientific, legal, ethical and societal information and with engagement opportunities, and thus to support better informed decision-making related to cell and gene-based therapies. • To facilitate better decision-making at key points in development of new therapies and thus enable improved product development, by providing the research community and regulatory and healthcare authorities with an information source on the practical steps needed for cell and gene therapy development. To achieve our aims, EuroGCT will adopt a highly structured system for coordinated management of information related to cell and gene therapy development and, from this, will implement an ambitious programme of online and direct stakeholder information provision and engagement. All outputs will be delivered in 7 European languages, to ensure broad accessibility, and will be rigorously evaluated against measurable objectives throughout the project duration. The proposed consortium comprises leading cell and gene therapy-related organisations and basic and clinical research labs across Europe, including new member states; together with experts in product development, ethical, legal and societal issues, and in evaluating clinical outcomes; patient representatives; and science communicators. It thus is uniquely placed to develop a world-leading cell and gene therapy information resource and to meet the challenge outlined in Topic SC1-HCO-19-2020.

Disruptive technologies for bone regeneration must be able to tackle complex fracture environments which have developed into non-union bone defects. These types of fracture are common and increasingly prevalent when considering the rise in osteoporosis cases. Bioengineered bone graft systems need to be able to guide the regrowth of new bone into substantial voids and therefore implants pre-seeded with mineralising cells are of significant clinical interest. We will implement a surgical co-administration of two robust technologies 1) a granular graft material with a highly osteogenic coating that presents relevant biologics very efficiently and 2) pre-differentiated osteogenic adipose mesenchymal stromal cells (MSCs) that together will underpin efficient bone regeneration. Within the project we aim to take these two technologies into GMP and ISO rated manufacture as required for any clinical therapy. We will then implement these therapies in pre-clinical studies to obtain efficacy and safety data to support a full clinical trial application. The novel technologies will be developed into a new medical device and a new cellular therapy with pre-clinical validation for their co-administration. This modular application of two highly advanced therapies is itself highly novel in terms of clinical strategy and by the end of the project we aim to have made the required regulatory and technical developments to submit them for clinical trial. In parallel to the core therapy we will expand the therapeutic pipeline by replacing the granular graft with 3D printed polymeric scaffold, again including including a highly osteogeneic coating, as a carrier for the cell therapy. Targeting even larger bone defects, this scaffold will be co-administered with the cellular therapy in pre-clinical efficacy studies.

Many human diseases, including cancers and inflammatory disorders, are associated with the production of ‘circular DNA’ from chromosomes. These molecules have potential as biomarkers, and in the case of cancers are potential drivers of disease progression. However, the technology for detecting circular DNA and for creating disease models is lacking, meaning we cannot explore their potential use in diagnostics. CIRCULAR VISIONs goal is to explore the new opportunities circular DNA creates in early diagnosis and monitoring of disease, particularly screening, and to create an experimental system to understand the link between disease and circular DNA. CIRCULAR VISION will explore this brand new territory by creating highly sensitive whole genome screens for circular DNA that correlate with disease, using lung cancer (LC) and inflammatory bowel disease (IBD) as model examples. We develop and combine novel methods in molecular biology, microfluidics, DNA sequencing and bioinformatics in order to identify new diagnostic markers. Such markers for IBD and LC will then be adapted to clinical diagnosis and prognosis using advanced image analysis and cytometry methods. Finally, CIRCULAR VISION will show the causal link between circular DNA and cancer, by producing disease models with oncogenes on circular DNA. CIRCULAR VISION assembles key pioneers in the emerging field of circular DNA with leading clinical experts and key commercial players in cytometry and genomics. We are convinced that our technology has broad applications in early noninvasive diagnosis of cancer and monitoring of inflammatory diseases. We believe our technology will lay the foundation for future research into circular DNA biology and spur future drug development.

FLEXPOL aims to develop a pilot line for the production of a cost effective antimicrobial (AM) adhesive film for its use in hospitals. The obtained adhesive film will inhibit growth of a wide range of microbes and will be suitable for high-touch surfaces, providing a durable protection with good resistance. It will assure the highest level of hygiene and patient safety, reducing the use of disinfectants. These objectives will be achieved, using a multi-functional approach combining prevention of adhesion with killing of microorganisms, by means of essential oil (EO) emulsions embedded in a micro and nanopatterned polypropylene matrix. FLEXPOL covers the following key aspects: -It addresses the development, upscaling and demonstration in a relevant industrial environment of the production of films with AM, biocompatible and anti-adhesive properties. Existing extrusion and nanoimprinting pilot lines will act as the starting point in which new additives based on blends of EO will be incorporated. -Previously validated technologies constitute the basis of the approach. These technologies will be extended to large scale production and demonstrated in a real operational environment. The pilot line will include real time characterization for inspection of the film at the nanoscale. -Robustness and repeatability of film fabrication and its behavior in a real environment will be studied. The effectiveness of the solution will be compared with standard protocols. -Materials are chosen according to their cost for large-scale application. Productivity and cost of the fabrication process will be analyzed attending to energetic optimization of the product fabrication and the raw material cost. -Access to the pilot line for AM films in this or a different application will be ensured to European Industries at a cost that promotes technology transfer. -Non-technological aspects key for the marketing of the product (such as regulatory issues, HSE aspects, LCA...) are considered.