The management and reconstruction of bone defects is a significant global healthcare challenge. While autografts offer ideal compatibility, they are often not suitable for large bone defects, and allografts suffer from potential immunorejection.The limited efficacy of conventional treatment strategies for large bone defects and the increasing aged population, has inspired the consortium to propose a SMART RESORBABLE BONE (SRB) IMPLANT embedding stem cells and bioactive agents with the aim of a controllable and fast restoration. The proposed solution includes 3D printed medical grade polymers enriched with electrospun fibers (for increased mechanical properties) that can be customized for patient physiology, pathology, and gender. The scaffold design will ensure easy and minimal Injury placement, and will embed different sensors for monitoring e.g. pressure, pH value and temperature based on biocompatible conductive inks. The smart implant will thus be able to provide vital information of implant performance in terms of bone growth and infection/inflammation. The proposed method is unique because it includes a customized smart implant (3D printed parts with adjustable sensors and communication electronic system), together with tissue engineering methods i.e. in-vitro programming of stem cells for embedding into the smart implant. The proposed solution introduces an innovative regenerative chain, from early testing and characterization (identification/adjustement of the proper specifications) and embedding regenerative stem cells and particulate bioactive agents into the smart implant in preclinical research (in-vitro). The in vivo proof of concept of SBR solution will be tested in (large animal model) preclinical studies within the scope of the project. Finally the regulatory and commercialization strategy on how to further explore the proposed concept and deliver it for clinical testing will be elaborated.

VIVID is a project on the Clinical Validation of In Vivo Imaging for Detecting Immune Dynamics. Optimising cancer treatment is a challenge, especially with combination therapies and patient variability. The ability to study cell migration in a quantitative and non-invasive manner in vivo, of endogenous cancer-fighting immune cells and administered therapeutic cells is essential for biomarker-driven and personalised clinical trials. Our imaging agent, BEACONs, allow for multimodal, quantitative imaging of cell populations; here with quantitative 19F MRI and fluorescence. This project will demonstrate and validate the feasibility of cell tracking using multimodal imaging and increase the maturity of BEACONs (to TRL 5-6) through a first-in-man clinical trial in current cancer standard of care. Our specific objectives are to 1) Set up a clinical trial of interest to large pharma, here the imaging of labelled immune cells in a neoadjuvant setting; 2) Build a business plan and create a spin-off; 3) Ensure that any new IP is protected; 4) Perform outreach towards patients and end-users. The potential societal impact of using BEACONs includes being able to assess and adapt complex therapies in major diseases such as cancer organ transplants, allowing a more targeted treatment and reducing patient burden such as negative side effects of ineffective treatment. The economic benefit of using BEACONs is large, while also reducing animal use, and enabling early assessment of cell therapies and cancer therapies. VIVID allows the application of our technology in a new field -that of personalisation of cancer therapy- aside from cell therapies, increasing our potential customer base (oncology drug market expected $285B in 2023).

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 lymphatic system and lymph nodes (LNs) are an integral part of our adaptive immune system and many tumors exploit lymphatic vessels to spread and colonize downstream LNs. Tumor-LN-oC aims to offer a comprehensive solution for a robust, automated tumor-lymph node-on-chip platform that will connect primary surgically removed human tumors and LN tissue from the same cancer patient. This will allow us to study the interaction of primary tumors with lymph nodes, identify their chemical signature, and offer personalized treatment relying on molecular characterization of lymph node metastasizing cells. The project will significantly advance the fields of microfluidics, cell biology, cancer biology, physics, and computer programming and software development, by pursuing the following objectives: a) To introduce novel designs and develop robust, automated microfluidic chips optimized for tumor cell and LN culture enabling the study of their crosstalk, b) To integrate Quantum Cascade Laser based mid-IR spectroscopy for specific chemical signatures, c) To molecularly characterize both migrating tumor-derived cells attracted to the LN and the soluble signals driving migration, d) To demonstrate an advanced image analysis and signal processing platform using deep learning algorithms facilitated by a micro-optics module to monitor in real time the cells migration, e) To integrate all Tumor-LN-oC technologies in an automated platform prototype incorporating interfaces compatible with existing laboratory equipment. The Tumor-LN-oC platform, will be developed at TRL5 and will be validated using real patient samples. Regulatory pathways, standards and requirements compliance will be considered in order to facilitate exploitation and early market entry. The consortium encompasses key – industrial partners and experts in the aforementioned interdisciplinary fields and is expected to have substantial impact in EU’s economy and healthcare.

Polycystic Ovary Syndrome (PCOS) is the most prevalent, chronic endocrine-metabolic disorder of adolescents and young women (AYAs), affecting 5-10% of AYAs worldwide. It is the most frequent cause of anovulatory subfertility. There is no approved therapy for PCOS. Standard off-label treatment with oral contraceptives reverts neither the underlying pathophysiology nor the associated co-morbidities Pilot studies have generated new insights into the pathophysiology of PCOS, and have thus led to the development of a new approach wherein the PCOS phenotype is reverted without side effects. The novel medication is a fixed, low-dose combination of two insulin sensitisers [Pioglitazone (Pio), Metformin (Met)] and one mixed anti-androgen and anti-mineralocorticoid (Spironolactone (Spi)] within a single tablet: SPIOMET SPIOMET4HEALTH will test, in a multicentre Phase II trial, the additive effects of each SPIOMET component, on top of lifestyle measures in AYAs with PCOS. SPIOMET aims at normalising the ovulation rate and endocrine-metabolic status via the reduction of hepato-visceral fat excess, in an early phase of the disorder. This approach is expected to reduce the risk of morbidity (including subsequent anovulatory subfertility), to improve the quality of life, and to lower the economic burden on European healthcare systems. The consortium clusters the experts from key research groups working on PCOS in AYAs, across Europe. The design of SPIOMET4HEALTH foresees that the patients themselves will be engaged over the entire timespan of the project, and will also contribute to the ultimate study evaluation. The update and validation of PCOS-specific Patient Reported Outcome Measures (PROM) will provide the first large-scale evidence on the psychosocial benefits of the tested treatments. The collective evidence from SPIOMET4HEALTH, once completed with economic modelling, will lead to conclusions that inform sound decision-making about PCOS across European healthcare systems.