The launch of a novel drug to the market is preceded by clinical testing and validation both on animal in vitro and in vivo models. Animal models used in drug development have known methodological drawbacks leading to the failure of drugs. Further, animal tests are associated with ethical issues. Moreover, a strong bias in in-human testing still overlooks major population groups e.g. children, women, different ethical groups. It is estimated that 197,000 deaths per year in the EU are caused by Adverse Drug Reactions (ADRs) and the total cost to society of ADRs is €79 billion. The emerging Organ-on-Chip (OOC) field, an alternative to animal test, brings great potential for safe testing and validation: An OOC-systems consists of a 3D-microstructured channel network embedded on a small plastic device that simulates the mechanics and physiological response of an entire organ or organs. Project UNLOOC will develop, optimize, and validate a multitude of ECS-based tools to build OOC-models to replace animal and in-human testing. UNLOOC aims to combine three important characteristics for routine use of OOC models, i.e platforms that combine ECS-based technologies with established biological material, capitalize on AI, parallelized test set-ups allowing efficient high-throughput demands, and standardized procedures enabling reliable results. UNLOOC will develop ECS-based hardware and software tools and validate them in five Use Cases (UCs) performed in 10 European countries. The applications developed and validated will be used by academia and pharma industry to drive drug development, create cosmetics without animal test, personalized medicine and gain new insights into disease. Given the large OOC market, these solutions have great economic value, on average it would result in cost reduction of up to $169M and $706M per new drug reaching the market and will put Europe at the forefront of this booming research field (see impact section for details).

Patients with cancer often have to make complex decisions about treatment, with the options varying in risk profiles and effects on survival and quality of life. Data-driven decision-support tools (DSTs) have the potential to empower patients, support personalized care, improve health outcomes, and promote health equity (optimal decisions also for underserved groups). However, DSTs currently seldom consider quality of life or individual preferences, and their use in clinical practice remains limited. To address these challenges, the 4D PICTURE consortium will further develop a promising methodology, MetroMapping, to redesign care paths that include novel DSTs. We will better predict treatment outcomes by developing innovative algorithms and incorporating patient experiences, values and preferences, using AI-based models. In co-creation with patients and other stakeholders, we will develop data-driven DSTs for patients with breast cancer, prostate cancer and melanoma. We will evaluate these DSTs as part of MetroMapping as well as stand-alone, to ensure their sustainability as well as addressing social and ethical issues. We will explore the generalizability of MetroMapping and the DSTs to other types of cancer and across other EU member states. Improved care paths integrating comprehensive DSTs will empower patients, their significant others and health care providers in decision making, and strengthen care at the system level by improving resilience and efficiency. Whereas the 4D PICTURE consortium includes leaders in modelling, AI, decision making, citizen science, service design, ethics, risk communication, and policy making, this project will impact clinical practice and science across Europe and beyond.

VASTO Proof of Concept aims to develop and test an innovative microfluidic-based platform, which allows to evaluate the efficacy of different cell immunotherapy strategies against solid tumours. For this aim, we propose to microfabricate 3D solid tumour organoids with an aberrant microvascular network provided from the explant of human vessels. Although there are other different vessel-on-a-chip and/or microvascular network formation approaches that use in vitro cell monolayers, we are not aware of any solution covering human ex vivo blood vessel platform as it is proposed here. Therefore, we aim to recreate the existent mechano-chemical barriers characteristics of the tumour microenvironment in solid tumours with this novel ex vivo platform. With this technology, we can define a method to evaluate the efficacy of different immunotherapy-based strategies. Specifically, we focus on studying the effectivity of different Chimeric Antigen Receptor (CAR)-T cell therapies in solid tumours. Hence, the development of VASTO harbours the interest of CAR-T manufacturers to test these cell therapies against solid tumours. We will be able to asses CAR-T cell vascular extravasation, penetration into solid tumours and the CAR-T efficiency for tumour elimination. In addition to its applicability to liver cancer, the acquired knowledge in VASTO also could be extrapolated to any other kind tumours, but also in the development of an ex vivo platform for research in regenerative processes, by incorporating organoids from healthy donors, instead of malignant cells, and promoting functional vasculature, instead of aberrant one. Therefore, this human ex vivo platform will launch a new product to the market very attractive for clinical labs and companies, reducing animal experiments and providing a more reliable alternative for testing different therapies against tumours and approaching a more personalized patient-like model.

Compared to the pace of innovation in electronic consumer products, the pace of innovation for medical devices is lagging behind. It is the overarching objective of Moore4Medical to accelerate innovation in electronic medical devices. Moore4Medical emerging medical applications that offer significant new opportunities for the ECS industry including: active implantable devices (bioelectronic medicines), organ-on-chip, drug adherence monitoring, smart ultrasound, radiation free interventions and continuous monitoring. The new technologies will help fighting the increasing cost of healthcare by: reducing the need for hospitalization, helping the development of personalized therapies, and realizing intelligent point-of-care diagnostic tools. Moore4Medical will bring together 68 specialists from 12 countries who will develop open technology platforms for these emerging fields to help them bridge “the Valley of Death” in shorter time and at lower cost. Open technology platforms used by multiple users for multiple applications with the prospect of medium to high volume markets are an attractive proposition for the European ECS industry. The combination of typical MedTech applications with an ECS style platform approach will enhance the competitiveness for the emerging medical domains addressed in Moore4Medical. With value and IP moving from the technology level towards applications and solutions, defragmentation and open technology platforms will be key in acquiring and maintaining a premier position for Europe in the forefront of affordable healthcare

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.