Due to population lifestyle changes, i.e. obesity, diabetes and aging population, chronic wounds (CW) which fail to follow the typical healing process is a major medical socioeconomic challenge. Current wound management is clearly insufficient and advanced therapies failed in keeping their promise of reliable skin regeneration. The aim of FORCE REPAIR is to develop a smart and multifunctional wound dressing providing pro-regenerative environment and mechanical stability to treat CW. Thus, FORCE REPAIR will combine state-of-the-art technologies in a biological scaffold tailored to patient’s needs: (1) Antibacterial and bioadhesive bioink with antibiotics and anti-inflammatory loaded nanocapsules, (2) Elastin like polypeptides promoting innervation and vascularization (3) Wharton Gel Complex preventing oxidative stress and boosting key extracellular matrix proteins. Also, the dressing activated by UV light will induce contractile force to help wound closure and activate skin regeneration. A customized 3D bioprinter with a user-friendly 3D trajectory software will help to strategically placed the biological compounds to timely address and mitigate the degenerative process occurring in CW, i.e. infection, inflammation, tension forces to promote skin regeneration. The 3D printed dressing will be tested in relevant in vitro model with a human exudate library and testing relevant key healing steps (i.e. re-epithelization, angiogenesis, cell proliferation…). Selected candidates will be tested in vivo on pig CW models and mice with bacterial infection. To ensure translation to clinical practice and reach patients, regulatory framework, HTA and a business model will be defined for a viable exploitation strategy that will decrease economic burden of wound care management and improve patients’ QoL. Finally, to ensure market acceptance health professional will guide the development of FORCE REPAIR to offer a dressing that treat efficiently CW and can be used by medical staff.

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 blood-brain barrier (BBB) is a major obstacle in treating diseases of the central nervous system (CNS) such as Parkinson's, Alzheimer's, Schizophrenia and brain cancer, affecting 180 million Europeans with less than 5% of current candidate drugs effectively reaching the brain. NAP4DIVE strives to revolutionize the traditionally expensive and inefficient drug development for these diseases by establishing advanced non-animal alternatives for testing and predicting nanoparticle (NP)-based drug delivery across the human BBB. This approach aligns with EU and global initiatives to reduce animal testing and advance human-based biomedical research models. The project will develop two complementary non-animal tools: a high-throughput BBB-on-Chip and an in silico model based on machine-learning (“NP Design Simulator”). A digital repository of optimized nanoparticle designs “NP Design Library” will be created to gather publicly available and newly obtained NP characterisation data, specialised for BBB delivery. The Design simulator screens thousands of NP designs to recommend the most promising ones, which will be tested in vitro on the microfluidic BBB-on-Chip with real-time measurement of barrier integrity. The accuracy and physiological relevance of both tools will be validated by the pharmaceutical partner through comparison with clinical and pre-clinical data. NAP4DIVE tools will reduce animal use in CNS drug development by up to 95% while saving 30 % of costs. By identifying nanoparticles for cross-BBB drug delivery and offering avenues for new effective treatment options, NAP4DIVE addresses one of the most pressing healthcare challenges of the century. A comprehensive HTA will demonstrate market readiness and cost-effectiveness of the tools, an ethical assessment will analyse harm reduction and engagement with regulators and policy makers will promote non-animal alternatives in preclinical testing on a larger scale.

Safe and Sustainable by Design approach requires an entire life cycle monitoring of toxicity of chemicals. However, current testing systems cannot mimic the exposure conditions related to each step and are not compatible with downstream in silico analyses. New sets of instrumentation that enables modular testing capacities with integrated data bridging and progressive in silico model development systems are needed. TOXBOX will provide a device based on a prototype developed in a H2020 project, PANBioRA, with a flexible microfluidic and instrument architecture to provide a plug and play testing platform to ease accessibility and interlaboratory validation. The system will incorporate the following tests, with modifications for each step of life cycle: automated cytotoxicity and genotoxicity tests, connected barrier/metabolic tissue couples with cytokine and real-time electro-chemical read-outs, flow cycle modules with environment mimicking conditions, a testing module based on zebrafish embryo with mechanical stimuli. The system will be validated using metallic 2D structures and nanoparticles, biocides, and known endocrine disruptors. Custom made functional polypeptides (novel biocides) will be used to cover the design phase. Progressive in silico models for long term effects will be iteratively developed and used to predict each new group to be tested until good predictability is achieved with new chemical formulations (comprehensive risk assessment). A data management platform that enables interfacing with the available databases will be developed. After interlaboratory validation of the device by 4 partners, a standardization folder will be prepared, to make the device available for testing with accessibility at all stages of material life cycle assessment to different stakeholders. TOXBOX aspires to bring forth an instrument that will provide reliable toxicity data in relevant conditions for each chemical and enable reliable in silico model development.

Despite advances in organ transplantation technology, there is still a huge shortage of transplantable organs. Yearly, 25% of patients with end-stage liver disease on the donor waiting list die, emphasizing the need for alternatives to organ donations, such as bioprinting. Bioprinting presents a promising approach for creating organs from scratch, yet, it faces significant hurdles due to technical and biological challenges, combined with lacking standardized procedures and materials. In NEOLIVER, we will develop large, dense, and vascularized fully functional bioprinted constructs suitable for transplantation. We will achieve this by establishing a GMP-conform manufacturing line for standardized production, ensuring unparalleled quality and safety for future patients. More specifically, by using patient-derived organoids and supporting cells including endothelial cells, we will generate millions of multicellular spheroids as building blocks for bioprinting. Through laser induced forward transfer (LIFT) bioprinting techniques we will create a vascularized liver construct via precise spatial deposition of spheroids and vessels at high density. By integrating this technology with extrusion-based bioprinted vessels for blood supply, we will generate the world's first autologous bioprinted liver, ready for transplantation. To show the safety and efficacy, we will transplant the bioprinted liver constructs in immune-deficient pigs. This, combined with a clinical validation plan, upscaling strategy and Health Technology Assessment (including patient acceptance), will prepare the bioprinted liver constructs for first-in-human trials. Thus, NEOLIVER presents a disruptive alternative to donor organs for patients dealing with end-stage liver disease.