This project will commercialize P-TEV - a unique personalized tissue engineered vein for the treatment of patients with severe Chronic Venous Insufficiency (CVI). CVI is a progressive medical condition in which the valves of the deep veins of the leg are not functioning properly. The most severe stage is CVI with leg ulceration. No effective treatment is available, and a large number of patients would directly benefit from venous vascular surgery. These patients cannot be cured today because no suitable grafts for replacement of the dysfunctional venous valves have yet been developed. There are no synthetic products which could replace the function of the bicuspid valves found in the leg veins and the risks associated with allotransplantation are too high. VERIGRAFT’s technology is the first one positioned to break this paradigm and fill the existing market gap. The technology allows the personalization of blood vessels by de- and recellularization. In short, a donated tissue is decellularized, removing all immunogenic donor cells and DNA. This results in a clean extracellular matrix scaffold with intact 3D structural properties. Subsequently, this scaffold is seeded with the patient´s own cells, derived from a small sample of peripheral blood. This unique technology turns an allogeneic (“foreign”) tissue into an autologous (“personalized”) one and thus avoids transplant rejection without the need for immunosuppression. The clinical proof-of-concept for P-TEV is established. The project will include the clinical study and GMP process development that will grant VERIGRAFT market access by 2019 and serve as a steppingstone to marketing approval by the European Medicines Agency. The EU-added value of the project is unparalleled, as it constitutes a breakthrough in one of future medicine's most promising fields – advanced personalized regenerative medicine, bringing significant long-term budgetary relief to healthcare systems.

The 4-Deep Brain Reconstruction, 4-DBR consortium aims at generating a brand-new technological approach to regenerate brain affections that occurs in neurological disorders. With 180 million affected people and an economic burden of 798 billion euros/year, Europe needs a radical leap in the future. The complexity of the human brain has condemned every past attempt at regeneration because incomplete technologies did not allow for a full recapitulation of the brain properties and any one of them missing jeopardized the functionality of the whole. There can't be any incremental solution for brain damage, the technology must be all-in. 4-DBR will focus on developing an implantable 4D reconstructed brain able to recapitulate all brain properties: a complex architecture of neuronal cells integrated in a complete blood circuitry, that will be complemented with an integrated opto-stimulator to induce correct specification and integration of neurons. 4-DBR integrates 6 technological leaders from complementary fields who will unite to develop the components of reconstructed-brains: laser-assisted bioprinting of pre-differentiated neurons with their native decellularized brain matrix, extrusion bioprinting of vascular system, in vitro blood-brain-barrier reconstruction and a tissue integrated wireless-controlled stimulating optoelectrical chip. These 4 components will then be combined into a transplantable reconstructed brain that will be tested in a small animal model of Huntington’s disease. While a first prototype will be delivered in 36 months, the vision unifying 4-DBR expands way further. Therefore, the project will put into action a strong dissemination and exploitation plan: horizontally, 4-DBR will ensure the uptake of the generated methods to strengthen Europe’s technological actors; vertically, 4-DBR will thrust the reconstructed brain approach up in the development ladder to potentially generate in a 10-year span a therapy to change the lives of many patients.

The main objective of Training4CRM is to train a new generation of 15 highly inter-disciplinary early stage researchers at the highest international level and quality, who will be immediately employable in both the academic and industrial sectors due to their highly sought after cross- and interdisciplinary insights and expertise. Training4CRM addresses existing gaps within Cell-based Regenerative Medicine for treatment of neurodegenerative disorders (e.g. Parkinson´s, Huntington´s, Epilepsy), which occur as a result of progressive loss of structure, function and/or death of neurons in the brain. The disorders have a high prevalence and are associated with impairments and disabilities with high emotional, financial and social burden. New scientific discoveries and technologies are needed, and Training4CRM sets out with the ambition to educate and train students within and across different scientific disciplines to be able to master the design, fabrication and testing of completely new tools and materials within the fields of: Micro- and Nanoengineering (nano/microstructures, 3D scaffolds and 3D lab-on-a-chip devices of different materials, geometries, architectures and properties, wireless electronic components; Biotechnology (human stem cells, human induced pluripotent stem cells, optogenetics, tissue engineering; Pre-clinical studies for the purpose of investigating in vivo, in experimental animals, how the developed cells, materials, structures affect the animal at the physiological and behavioral levels, unravelling the therapeutic effects of the developed strategies.

Clinical need: 10% of the population worldwide is affected by chronic kidney disease (CKD) and millions die each year because they do not have access to treatment. Giving global shortage of kidney donors, the vast majority of patients rely on hemodialysis (HD). Over 2.6M people worldwide currently receive HD to stay alive, yet this number may only represent 10% of people needing treatment. Solution: Up to 70% of current arteriovenous grafts (AVG) fail in the first year after implantation. This is primarily due to thrombosis, luminal scar formation, and infection. In our ground-breaking new AVG, biomimicking zwitterions prevent thrombosis, drug delivery prevents scar formation and infection, and an ECM coating ensures fast tissue integration allowing early HD. Smart: TELEGRAFT comprises two diagnostic tools to monitor and prevent device complication. Pressure transmitters are used to monitor blood flow and optical sensors to detect inflammation and infections. The data is processed by AI machine learning models and displayed in an easy to understand dashboard for healthcare professionals. The data allows online telemonitoring and consultations by remote healthcare professionals. This makes home dialysis safe for patients, even in areas with poor infrastructure, where patients live far from HD clinics. Surgical implantation: The TELEGRAFT system will be demonstrated in an operational environment through a 2-stage randomized clinical trial enrolling 60 patients at 5 hospitals across Europe and through a home HD field study. Resource constrained setting: (1) In low and middle income countries, TELEGRAFT will substitute complicated and expensive kidney transplantation and allow simpler and cheap implantation of AVG for HD. (2) TELEGRAFT is the only solution with diagnostic tools allowing real-time online detection and remote monitoring of complications and device failure. This allows transition from HD at the hospital to the resource constrained home setting.