In 2020, the cell culture market was valued at $19 billion USD, with consumables comprising more than 60% of the market. The emerging 3D cell culture provides lucrative business opportunities for consumables and tissue test models, but current technology and market supply lack an easy and reliable tool for the uncomplicated creation and cultivation of vascularized and perfusable artificial 3D tissue. The current 3D cell culture consumable market offers only well plate inserts and organ-on-a-chip systems for generating 3D tissues, which are limited regarding tissue mimicry and complexity. Bioprinting, while promising, is still unreliable for reproducible vascularized tissue engineering. The EIC Transition Proposal Vasc-on-Demand aims to fill this gap by providing three easy-to-use laboratory products for the generation and cultivation of perfusable vascularized 3D tissue: 1. BasicVasc: An all-in-one bioreactor consumable for generation and cultivation of perfusable tissue culture 2. EasyVasc: Prefabricated ready-to-use vessel channel networks without cells 3. CompleteVasc: Prefabricated matured cell-containing vascularization EasyVasc and CompleteVasc both build on the BasicVasc technology. Therefore, BasicVasc will be advanced for high-throughput production of precisely manufactured structures to be ready for the market. The other products will be fully developed and characterized to allow improved vascularized tissue production with even more advanced and simpler ready-to-use systems. This grant will be carried out by a highly motivated team with synergistic expertise in technology, product engineering, and business development, working towards the foundation of a start-up for the commercialization of the technology. The proposed Vasc-on-Demand has the potential to simplify the development of sophisticated test models for research and pharmaceutical approaches like drug testing, leading to reduced animal trials and development costs.

The e-Intervention Enhancing Mental Health in Adolescents project, IMPROVA, will co-design, pilot, evaluate, and facilitate the upscaling of a modular eHealth intervention platform that aims to improve mental health and well-being, early detect mental health problems and prevent common mental disorders in adolescents. The IMPROVA consortium includes an international and inter-disciplinary group of researchers and practitioners from health, educational and social sciences in addition to computer scientists, a teacher association and policymakers. The IMPROVA online platform will be co-created with stakeholder groups, including adolescents, parents, teachers, school health professionals and policymakers based on materials already designed and tested in more than 20 projects carried out by the consortium members. The platform will include components for adolescents, parents, teachers, and school health professionals in complementary and synergistic modules. After a series of pilot testing sessions, IMPROVA will be implemented by conducting a randomized Stepped Wedge Trial Design (SWTD) in secondary education schools randomly selected in four countries (France, Germany, Romania and Spain), including 12,800 adolescents. Effectiveness, cost-effectiveness and cost-benefit will be calculated. Using implementation science methodology, IMPROVA will co-design with policymakers and stakeholders transferable evidence-based practices, methodologies and guidance for upscaling of the IMPROVA platform. IMPROVA aims to provide stakeholders and policy makers with an evidence-based, innovative, large-scale, comprehensive intervention, and a scale-up plan to promote mental health and prevent mental disorders in adolescents; empower adolescents and families to make better decisions regarding their mental health; and provide schools and the community with tools to achieve a society with better mental health and lower stigma.

The miniNO project aims to identify the key causative mechanisms of the lifelong multimorbidity associated with preterm birth. Prematurity is associated with alterations in the maturation of the hypothalamic-pituitary-gonadal axis, and specifically with its transient activation during infancy, known as minipuberty. miniNO will study for the first time the association between premature birth and alterations in minipuberty and infantile nitric oxide (NO) signaling in the brain, and comorbidities that appear later on in life. The project is based on robust preclinical data and previous clinical studies, and will exploit data concerning premature birth and minipuberty in existing cohorts as well as newly created cohorts. We will identify the molecular association between NO deficiency, altered minipuberty and multimorbidity combining mental (e.g. autism, social cognition, learning and memory impairments) and non-mental disorders (e.g. anosmia, hearing loss, metabolic abnormalities, cardiovascular impairements and infertility) as well as gender, environmental and lifestyle factors. For this, we have assembled a unique interdisciplinary consortium of renowned basic scientists (neuroscientists) and clinicians (pediatric and adult endocrinologists, psychiatrists, geneticists) and an SME to implement the project results. By validating the causative mechanisms of the multimorbidity related to preterm birth, we will propose and develop novel diagnostic and preventive tools, including screening tests for biomarkers and newly identified genetic factors, for altered minipuberty, thus paving the way to personalized treatment and new therapeutic options very early in life. miniNO is expected to improve the quality of life of millions of prematurely born individuals and reduce the financial and societal burdens they impose.

A fundamental limitation with current approaches aiming to bioprint tissues and organs is an inability to generate constructs with truly biomimetic composition and structure, resulting in the development of engineered tissues that cannot execute their specific function in vivo. This is perhaps unsurprising, as many tissues and organs continue to mature postnatally, often taking many years to attain the compositional and structural complexity that is integral to their function. A potential solution to this challenge is to engineer tissues that are more representative of an earlier stage of development, using bioprinting to not only generate such constructs, but to also provide them with guiding structures and biochemical cues that supports their maturation into fully functional tissues or organs within damaged or diseased in vivo environments. It has recently been demonstrated that such developmental processes are better recapitulated in ‘microtissues’ or ‘organoids formed from self-organizing (multi)cellular aggregates, motivating their use as biological building blocks for the engineering of larger scale tissues and organ. The main goal of micro2MACRO (m2M) is to develop a new bioprinting platform capable of spatially patterning numerous cellular aggregates or microtissues into scaled-up, personalised durable load-bearing grafts and guiding their (re)modelling into fully functional tissues in vivo within damaged or diseased environments. This will be achieved using a converged bioprinting approach capable of rapidly depositing cells and microtissues into guiding scaffold structures with high spatial resolution in a rapid, reliable, reproducible and quantifiable manner. These guiding structures will then function to direction the fusion and remodelling of cellular aggregates and microtissues into structurally organised tissues in vitro and in vivo, as well as providing medium-term (3-5 years) mechanical support to the regenerating tissue.

Tinnitus is the perception of a phantom sound and the patient’s reaction to it. Tinnitus remains a scientific and clinical enigma of iTinnitus is the perception of a phantom sound and the patient’s reaction to it. Although much progress has been made, tinnitus remains a scientific and clinical enigma of high prevalence and high economic burden. It affects more than 10% of the general population, whereas 1% of the population considers tinnitus their major health issue. Recent cohort studies show that tinnitus prevalence tends to increase over time and with older age. Assuming that there is no cure to be found, the prevalence estimates in Europe would double by 2050. A large variety of patient characteristics - including genotyping, aetiology, and phenotyping - are poorly understood, because integrated systems approaches are still missing to correlate patient`s characteristics to predict responses to combinatorial therapies. Although genetic causes of tinnitus have been neglected for decades, recent findings of genetic analysis in specific subgroups (gender and phenotype) have highlighted that bilateral tinnitus in men reached a heritability of 0.68. This heritability is close to autism, schizophrenia and Attention Deficit Hyperactive Disorder (ADHD). There is no current consensus on tinnitus treatment. UNITI’s overall aim is to deliver a predictive computational model based on existing and longitudinal data attempting to address the question which treatment approach is optimal for a specific patient based on specific parameters. Clinical, epidemiological, medical, genetic and audiological data, including signals reflecting ear-brain communication, will be analysed from existing databases. Predictive factors for different patient groups will be extracted and their prognostic relevance will be tested in a randomized controlled trial (RCT) in which different groups of patients will undergo a combination of therapies targeting the auditory and central nervous systems.