Partners
BRAV∃ brings together 14 different partners from six member states of the European Union. In line with the multidisciplinary spirit of the project, the consortium includes three university hospitals, four universities, three technological research centres, three SMEs, an international company. Here you can find information about all of them.
Spain 
The University of Navarra (UNAV) is a non-profit private university based at the southeast border of Pamplona, Spain. The Biomedicine campus comprises the School of Medicine, the Faculty of Sciences, the School of Pharmacy, the University Clinic of Navarra (CUN) and two research centres. CUN is a reference centre in Spain for several procedures, including Regenerative Medicine strategies. The Cellular Therapy Area (CTA) co-ordinates a multidisciplinary team of basic and clinical research in UNAV-CUN. CTA vision is to deliver new frontline treatments through interdisciplinary research into basic disease mechanisms and the application of novel therapeutic approaches and technology. The expertise of CTA includes state-of-the-art stem cell know-how (hiPSC derivation, growth, gene editing and differentiation), NGS (single cell and bulk RNAseq, ATACseq, ChiPseq, etc.) as well as small and large animal models of disease amongst others.
Principal Investigator: Dr. Felipe Prosper.
Main tasks in the proposal
At the scientific level, UNAV will be implicated in the design and carrying out of activities related to MEW-3D printing and hydrogel development and in vitro testing (WP3 and WP4 respectively), as well as hiPSC line gene editing (WP4), biocompatibility analysis of materials as well as testing of the maturation bioreactor prototype (WP5), which will be located at UNAV. We will have a transversal role in WP6, from the cellularization of the first BioVADs, to the characterization phase, especially related to NGS, structure and histopathology. UNAV will also participate in WP7 in the tissue analysis, surgery planning and histopathological analysis of BioVAD-transplanted hearts. Finally, UNAV will participate in WP8 (Exploitation & commercialisation strategy) and will lead and supervise the management of ethical issues and data management within the Consortium (WP8) as well as the Project coordination (WP10) and Communication and Dissemination activities (WP11).
The University of Zaragoza (UNIZAR) is the only public University of the Autonomous Region of Aragón, Spain and one of the oldest in Spain, created in 1542. The Aragón Institute of Engineering Research (I3A) is one of the research institutes at UNIZAR. Composed of more than 30 research groups and over 250 researchers, it is one of the biggest and more recognized research institutes in Engineering in Spain. Inside the I3A Division of Biomedical Engineering, the group of Applied Mechanics and Engineering (AMB) is considered one of the groups of excellence in Bioengineering in Spain. The AMB group has a large experience in the fields of modelling and simulation of continuous systems, with applications in tissue mechanics (bone, cartilage, ligaments and tendons, heart, blood vessels, eye), biological systems (remodelling, growth, morphogenesis), tissue engineering (scaffolds design, functionalization, de and re-cellularization), and, finally, cell processes (microfluidics, cell migration and differentiation, organ on chip).
Principal Investigator: Dr. Manuel Doblaré.
Website: www.unizar.es
Main tasks in the proposal
UNIZAR will apply its unique expertise and infrastructure to lead the biomechanical characterization of tissues and part of the modelling activities. As such, this is concentrated in WP2. In addition, this team will perform biaxial mechanical tests on acellular, cellularized and matured BioVADs (WP3 and WP6), as well as characterizing the IHD porcine hearts after BioVAD transplantation.
EBERS Medical Technology SL was established in 2009 as a spin-off company of the University of Zaragoza (Spain). EBERS develops and commercializes research equipment for cell culture and medical devices for ex vivo organ preservation. In the field of cell culture, EBERS bioreactors provide in vitro conditions that closely mimic the physiological setting cells experience in vivo. The main application of EBERS cell culture devices lies in the field of tissue engineering, where the company commercializes bioreactors —capable of providing flow, direct mechanical and electrical stimulation and hydrostatic pressure— as well as different kinds of culture chambers and accessories that can be used for the culture of tissues as muscle, bone, cartilage, tendon, ligament, skin and blood vessels, among others. Nowadays, EBERS commercializes its products all over the world through its distributor network and continues to develop new products as a fundamental part of its R&D strategy.
Principal Investigator: Dr. Pedro Moreo
Website: www.ebersmedical.com
Main tasks in the proposal
The main involvement of EBERS in the project will be in WP5 and WP6, in all the engineering tasks related to the incubator chamber containing the maturing BioVAD, and its monitoring. More specifically, EBERS will design and fabricate an incubator chamber to be used in combination with the bioreactor. Moreover, EBERS will also collaborate on the final integration and testing of the all the parts of the whole cell culture system. Given the capacity of this work to generate IP, EBERS also takes part in WP9.
Servicio Madrileño de Salud (SERMAS) is the administrative organisation that manages and integrates every public hospital and every public health system of the Regional Health System of Madrid. SERMAS is the legal representative of Hospital General Universitario Gregorio Marañón (HGUGM). HGUGM is the largest University Hospital in Spain. It is a public hospital under the Ministry of Health and the Community of Madrid direction, consisting on more than 8,000 professionals responsible for specialized medical care of an area with approximately 750,000 citizens. In 2009, Dr. Fernández-Aviles established the Laboratory for Bioartificial Scaffolds as the main translational cardiovascular research unit of the hospital. The laboratory consists of 14 multidisciplinar researchers including four senior researchers, three post-docs, four PhD students and several pre-graduate students, supported by four research technicians.
Principal Investigator: Dr. Franscisco Fernández-Aviles.
Website: https://www.comunidad.madrid/hospital/gregoriomaranon/
Main tasks in the proposal
Dr. Fernández-Aviles’ team is focused on the translation of cardiac regeneration therapies by combining in vitro, preclinical and clinical research, which will be essential to assemble BRAV∃. The group has key experience in the characterization of electrophysiological properties of cardiac tissues both in vitro, generated from human pluripotent stem cells, and in vivo, in animals such as pigs and in humans. The team will actively participate in WP6-WP7 and contribute to outreach the outcomes of the BRAV∃ project.
Leartiker is a private Technological Center focused in Polymer Technology located in the North of Spain (Xemein-Markina, Bizkaia). It belongs to the Basque Innovation system and to Mondragon Group. 24 highly qualified and motivated professionals conform Leartiker Polymer technology area, working in four specialization areas:
Medical devices: in close contact with hospitals and medical professionals, Leartiker designs, manufactures and tests medical devices for straightforward translation.
Lightweight and material substitution: Simulation of manufacturing process and structural behaviour is the core field of this area. Leartiker is focused in the development of material characterization protocols for further structural simulation procedures.
Fatigue in elastomers: an area in which Leartiker is a European reference in elastomeric fatigue characterization and simulations.
Additive manufacturing: material development for AM is the area of expertise of Leartiker. Leartiker is able to apply AM under GMP conditions, which will be of high relevance for this project.
Principal Investigator: Dr. Ane Zaldua.
Website: www.leartiker.com
Main tasks in the proposal
At the steering wheel of WP5, the main tasks in the project will be the design and definition of the production process of the “Bioreactor”. Leartiker will produce a prototype and will integrate it in the incubator chamber,. It will be also in charge of the monitoring of the mechanical deformation using Digital Image Correlations (DIC) systems. Finally, Leartiker will design and produce all the peripheral devices needed in all the process of the project. Given the capacity of this work to generate IP, Leartiker will also take part in WP9.
IBEC is a research institute covering most bioengineering fields, from basic research to medical applications, aiming to act as an international reference in this field. IBEC was established in 2005 by the Government of Catalonia, the University of Barcelona (UB) and the Technical University of Catalonia (UPC). Moreover, IBEC is one of the Spanish research centres of excellence awarded accreditation by the Severo Ochoa Excellence Programme, which recognizes excellence at the highest international level in research, training, human resources, outreach and technology transfer. IBEC is also member of the Barcelona Institute of Science and Technology (BIST). BIST is a multidisciplinary research institute formed by the alliance of seven top research centres in Barcelona committed to creating a collaborative environment of multidisciplinary scientific and training excellence.
Principal Investigator: Dr. Nuria Monserrat
Website: http://www.ibecbarcelona.eu/iPSCs
Main tasks in the proposal
Dr. Montserrat team is focused on the development of engineered human pluripotent stem cells and biomaterials, which will be essential to assemble BRAV∃. The group has also key expertise in stem cell biology and the cell mechanics which will be key to study the differentiation potential and maturation of human pluripotent stem cells to cardiac cell populations (such as cardiomyocytes, endothelial cells and fibroblasts). The team will lead WP4 and actively contribute from month 1 to WP3 and WP5. IBEC will participate in the communication activities planned in WP4 to outreach the outcomes of the BRAV∃ project.
Netherlands 
Eindhoven University of Technology (TU/e) is a research-driven university specializing in engineering science & technology. Its activities concentrate on strategic areas around the major societal issues, Energy, Smart Mobility, and Health. TU/e has over 10000 students (6600 BSc, 4100 MSc) and about 2000 research staff members, including and 1400 PhD students. TU/e is one of the first universities in Europe with a Department of Biomedical Engineering with a dedicated and complete undergraduate and graduate program.
The CardioVascular BioMechanics (CVBM) group of the BioMedical Engineering department (BME) of the Eindhoven University of Technology has leading expertise in an experimental and computational pathophysiological modelling. The group is headed by Prof.dr.ir. F.N. van de Vosse and a strong record in the development of technology consisting of computational modelling platforms and clinical measurement systems to predict outcome of medical interventions patient specifically and use this as a basis for clinical decision support systems in the cardiovascular domain.
Principal Investigator: Dr. Peter Bovendeerd.
https://www.tue.nl/en/research/researchers/peter-bovendeerd/
Main tasks in the proposal
TU/e will lead WP2 on electromechanical modelling for generation of a biomimetic BioVAD design. Together with project partner UNIZAR, a workflow will be generated for the in silico design of a 3D personalized BioVAD, accounting for long-term outcomes. First, an initial generic BioVAD design will be developed, serving as a point of departure for subsequent WPs. The design will be gradually be optimized once experimental data from other WPs becomes available. TU/e contribution builds upon extensive experience with finite element models of electromechanics in the healthy and diseased (infarction, conduction disorder) heart, models to describe change in cardiac size and tissue properties in response to changes in mechanical load, and (lumped parameter) models that describe the dynamics of the complete cardiovascular system including autoregulation and short- and long-term adaptation.
The University Medical Center Utrecht or UMCU is the main hospital of the city of Utrecht. It is affiliated with the Utrecht University and comprises the academic hospital, the faculty of Medicine as well as the Wilhelmina Children’s hospital. The Orthopeadics & Biofabrication group focuses on the development of novel approaches for osteochondral repair through the convergence and development of biofabrication technologies, including robotic dispensing, melt electrospinning writing and stereolithography. For this purpose, the group develops its own bioinks for printing, and tests them with different cell sources that have potential for clinical applications. The bioprinted constructs also are tested in vitro, in ex vivo (explants) osteochondral defect models and bioreactors to provide tissue maturation and validation as close as possible as that occurring in the in vivo situation.
The central research topic in the department of Cardiology (Experimental Cardiology laboratory) is cardiac regeneration, especially the use of human cardiac-derived progenitor cells, mesenchymal stromal cells and hiPS-derived cardiomyocytes or their secretions for cell-based therapies to regenerate the heart and improve cardiac performance. Moreover, advanced 3D models are being developed to mimic human cardiovascular diseases for mechanistic understanding and therapeutic usage. The research group has the expertise to perform all standard molecular/biochemical procedures, cell culture techniques, and has a broad expertise and facilities for pharmaceutical and molecular interventions in cardiac and atherosclerotic animal models.
Principal Investigator: Dr. Jos Malda.
https://www.umcutrecht.nl/en/Research/Researchers/Malda-J
Main tasks in the proposal
The activities performed in BRAV∃ by UMCU will be in WP3 and WP4. Concretely will be involved:
- 3D printing of cardio-conductive fibre-reinforced systems:
- Model-to-design translation, MEW printing, generation of composite systems and characterization.
- Compliance of the support and fixation region with model, ex vivo testing and adhesion
- Fabricate the mesh structures and plan the assembly of the support integrating the cell-free adhesive for a “patient-specific” BioVAD.
- Ex vivo testing of adhesiveness and affixation of the support to the heart
- hiPSC-derived cardiac cell production and characterization after cryopreservation of hiPSC-cardiac derivatives.
- Cardiac and vascular tissue formation capacity / compatibility with scaffolds/hydrogel.
- In vitro studies to assess the capacity of the fibre composite to induce cell orientation, support cell maturation and generation of functional viable cardiac engineered muscle.
AE Medicalis is a start-up focused on implantable electric motors and develops a percutaneous pump with its own algorithms. Therefore numerous engineers are available and can be used to contribute to the specifics of this project. The founders of AE Medicalis have worked in academia for numerous years and led the successful development of one of only two FDA approved LVAD’s for the treatment of advanced stage heart failure with over 15,000 clinical implants world-wide. Besides the academic responsibilities, they were responsible for engineering management, requirements and design, and intellectual property; and the development of implantable components and tools, system controller, physiologic algorithms including estimated flow and waveform algorithms, and transcutaneous energy transfer systems of various developments that led to a commercially successful LVAD, besides all the non-commercial developments that have been researched “en-route”.
Principal Investigator: Dr. Johannes Paulides
Main tasks in the proposal
Within the project BRAV∃, we will focus on controlling flow during the surgical heart procedure with flow control in order to allow a stabilized heart during the new cardiac muscle supply. The personalized side of this approach will ensure that the support is supplied at the needed locations, and with the correct shape and dimensions, so no engineered myocardium is wasted. This will allow the mechanoelectrical modelling to closely match the experimental biomechanical and electrophysiological data, down to the personalized level. AE Medicalis will contribute to WP2 by modelling the flow of the percutaneous heart pump to establish the influence of the device on the blood flow. Further, in WP5 AE Medicalis will undertake flow loop measurements on the percutaneous pump and will work on flow prediction algorithms; one important contribution will be the variation of the flow to minimize the heart movement. Finally, within WP7 we will assist with the training, surgery planning and transplantation. In this respect, the pump might be able to work both ways, to assist the heart following euthanasia, to simulate the hearts movement to allow an advanced electrophysiological analysis. AEMed will also implicated in the exploitation strategy of the project.
Belgium 
The University Hospital Leuven (UHL) is the largest university hospital in Belgium, and an integral part of the University of Leuven (KUL), founded in 1425 and thus one of the oldest universities in Europe. KUL is an institution for research and education with high international appeal. All programmes at this University are based on the innovative research of its scientists and professors. The Group of Biomedical Sciences consists of 14 departments and includes the Department of Cardiovascular Sciences. Interdisciplinary institutes cross the borders of these departments. The department of Cardiology is part of the Department of Cardiovascular Sciences and is at the forefront of clinical innovation in the management of acute coronary syndromes, advanced heart failure (resynchronization therapy, left and right ventricular assist device (VAD) development, cell therapy and cardiac transplantation), adult congenital heart disease and complex arrhythmogenic heart disease. It has participated in and initiated several clinical stem cell trials, and are actively developing novel cell‐based and hybrid interventions tailored to specific patient populations with advanced heart disease. It is also actively collaborating in a bench-to-bedside translational research approach with basic scientists based on our health science campus and focusing on myocardial functional and structural remodeling, vasculogenesis, and stem cell applications (including tissue‐engineered biomaterials, exosomes and microparticle approaches).
Principal Investigator: Dr. Stefan Janssen.
Main tasks in the proposal
KUL will mainly participate in the Electromechanical modelling for the generation of a biomimetic BioVAD design. It will bring in extensive expertise in 2D and 3D multimodal imaging of the normal and the diseased porcine heart. These functional, mechanical and electrical data are quintessential to convert the generic computational model into a specific model that will facilitate the initial in silico design of the porcine-specific BioVAD, leading WP7 This WP is focused on deep cardiac phebotyping and BioVAD in vivo assessment. . Also, KUL will be implicated in the BioVAD generation and Bioreactor maturation.
Germany 
The Department for Functional Materials in Medicine and Dentistry at the University Hospital Würzburg (UKW) is a materials research-focused department embedded in a clinical setting as part of the university clinic. Research activities comprise surface modification of functional materials for biointerface engineering, tailored bioactive polymer synthesis, biological evaluation of materials, design and preparation of artificial extracellular matrices and hierarchical biomaterials systems, and different biofabrication techniques with the focus on melt-electrowriting (MEW) as cell free and extrusion based bioprinting based on bioactive polymers as directly cell processing strategy. These interdisciplinary activities are performed by a team of chemists, biologists, engineers and materials scientists and structured in the five-research platforms cell-material interaction, bioactive inorganic scaffolds, Biofabrication, Artificial Extracellular Matrix, and Nano-Biotechnology
Principal Investigator: Dr. Jürgen Groll.
http://www.fmz.uni-wuerzburg.de
Main tasks in the proposal
UKW will mainly be involved and lead WP3 throughout all tasks and will devote a minor dedication in WP4 and 6. Dr. Groll has extensive experience in the development of polymer based materials for biomedical applications, such as fibre based materials with tailored surface chemistry or hydrogels that allows the functional embeding and release of proteins and cells. Recent work focuses on hydrogels that can be used as bioinks for bioprinting. Dr. Jüngst has been establishing and evolving bioprinting technologies at the department FMZ. For the extrusion bioprinting of hydrogels he has developed a model for the rheological evaluation and prediction of printability of bioinks. Regarding MEW, he has build up and installed several home made printing systems, amongst them a system that enables printing onto cylinders to generate tubular constructs.
Portugal 
iBET is a private non-profit research intensive institution with over 30 years of experience in developing innovative biopharmaceutical solutions. Key areas of expertise include the bioprocessing and in depth, characterization of Advanced Therapeutic Medicinal Products (ATMPs) such as stem cells and viral vectors for cell and gene therapy. iBET is a leading institution in the development of advanced cell models for pre-clinical research and regenerative medicine. iBET investment in the development of 3D culture systems spans for more than 20 years, competences covering areas such as liver, central nervous systems, cancer and cardiac tissue. In particular, the iBET team has been developed novel cell culturing strategies that recreate the appropriate environmental conditions excelling growth and/or differentiation/maturation of pluripotent and adult stem cells of human origin. iBET also contributes significant experience in the integration of Omics approaches such as proteomics, transcriptomics, metabolomics and fluxomics, supported by state-of-the-art MS technologies, as complementary analytical tools to bioprocess optimization and product characterization.
Principal Investigator: Dr. Paula Alves.
Main tasks in the proposal
iBET will lead WP6, which aims at generating and characterizing mature BioVADs. iBET will optimize protocols for BioVAD cellularization and maturation and will carry out the characterization of BioVADs at metabolic and proteomic level. iBET will also participate on the production and preservation of hiPSC-cardiac derivatives (co-leader of WP4), due to the expertise of the team on hPSC manufacturing including hPSC expansion, cardiac differentiation and maturation in bioreactors as well as on cell cryopreservation/storage, and on the preliminary BioVAD generation activities in WP5. iBET will participate in the communication activities planned in WP6 to outreach the outcomes of the BRAV∃ project.
Ireland 
Boston Scientific Ltd (BSL) is a leading innovator of medical solutions that improve the health of patients around the world. It was founded in 1979 by Pete Nicholas and John Abele, employs approximately 29,000 employees worldwide, generating an annual revenue of $9.0 billion revenue (2017), with approximately $1 billion of this invested in R&D (2017). Boston Scientific’s products and technologies are used to diagnose or treat a wide range of medical conditions, including heart, digestive, pulmonary, vascular, urological, women’s and men’s pelvic health, and chronic pain conditions. It continues to innovate in these areas and is extending innovations into new geographies and high-growth adjacency markets. In Ireland, Boston Scientific Limited is located at three locations, Galway, Cork, and Clonmel, and is one of the largest employers in the country. The Galway site is the largest facility in Boston Scientific, and has R&D and manufacturing functions. BSL is certified for manufacturing medical devices for the EU, US, Japan, and many other countries. As such BSL has wide experience and is very well placed for medical device development stages from needs & requirements definition, design, prototyping, benchtop testing, tissue testing, animal testing, cadaver testing, documentation, design reviews, manufacturing of devices, process development and validation, Regulatory submissions, to Clinical trials.
Principal Investigator: Dr. Aiden Flanagan
Main tasks in the proposal
BSL will be involved in WP5, WP6, WP7, WP9, WP10 and WP11. The main tasks and activities are developing pacemakers for use in the bioreactor tissue maturation stage and for in-vivo implantation and will be act as co-leader under WP9 supervising the possibility of commercialization of the new generated pacemakers.