FLAMIN-GO aims at developing an Organ-on-Chip technology for clinical trials on Rheumatoid Arthritis (RA). In RA, a number of unmet needs still persist particularly related to response/non-response of powerful but expensive drugs. Conventional clinical trials may address part of these challenges, but are time consuming, expensive and ethically ethically doubtful as part of the patients still fail to achieve disease benefits. Thus, the rheumatology community has a need for an alternative strategy that can deliver innovative trials. FLAMIN-GO develops a personalized next-generation synovia-on-chip, that, by effectively mimicking the complexity of RA joint, will allow performing personalized clinical trials-on-chip. The solution will be based on design and fabrication of a multi-compartment microfluidic platform, for 3D culturing and perfusion of all the disease-relevant joint tissues. It focuses on synovia and synovial fluid, which are the pathogenetic targeted tissues, but including immune system, who sustain the disease, and cartilage and bone which are the end damaged tissues, leading to permanent disability. Starting from individual patient biopsies, this model seeks to replicate RA joints, thus allowing to test and allocate the best on-market drug for that patient in 1-2 months starting form biopsy. When validated, the platform will also be a turning point for i) pharma by enabling screening of new drugs reducing costs, time, and animal testing and for ii) translational research for identification of new biomarkers or therapeutic targets. FLAMIN-GO consortium features a strong, well-balanced composition of hospital, academia and industry partners, who cover with complementary expertise the whole value chain. It gathers experts in the fields of rheumatology, material science, tissue engineering, nanotechnology, cell biology and 3D modelling, in a cohesive, transdisciplinary, multi-sectorial approach taking on the challenge to drive RA personalized care.

Chronic low back pain due to intervertebral disc (IVD) degeneration and osteoarthritis (OA) worldwide impact human health and well-being due to pain and impaired mobility. Non-viral gene therapy has great promise as safe and precision treatment to restore IVD and joint tissue health. However, the lack of accessibility of the affected cartilaginous tissues to drugs has inhibited progress in this field. We will finally fulfil the promise of non-viral gene therapy in these diseases. We will do this through educating 15 young researchers in 10 different countries in physics, quality by design (QbD), nucleic acid chemistry, nanomedicine, cartilage and IVD biology, ethics, entrepreneurship and academic transferable skills. This highly multidisciplinary team will exploit the potential of gene therapy in IVD and joint disease by taking a multi-faceted approach towards the delivery and activity of oligonucleotides and encoding nucleic acids (NA). Cell and tissue delivery will be achieved by nucleic acid modification, innovative nanocarriers and tissue targeting, supported by QbD. Ultrasound will for the first time be used to enhance NA tissue penetration and transfection, and to trigger local release from systemically administered endogenous albumin-NA conjugates. Imaging tools will be developed to monitor in vivo regeneration, saving numerous animal lives in the future. Moreover, we will set up an educational framework for embedding biomedical ethics in biomedical research and valorisation, providing a firm and sustainable basis for Responsible Research and Innovation for future biomedical science and technology. Participation of a patient organisation and a scientific organisation experienced in the dialogue with society, will ensure researchers at ease in communicating with different audiences. Hence CARTHAGO will deliver the agile scientists freely moving between sectors and firmly anchored in society, required to take science and innovation to the next level in Europe.

MIRACLE will take towards commercialization the first mid-infrared (MIR) arthroscopy probe for in-depth evaluation of articular cartilage enabling early diagnosis of degenerative joint diseases such as osteoarthritis (OA). The proposed device is intended for use during a minimally invasive surgery (arthroscopy). Currently, the surgeon’s decision-making is based on visual inspection and manual probing of the cartilage tissue which is highly subjective and of poor repeatability. Untreated or not-correctly treated joint injury will most likely progress towards OA, which will lead to joint pain, movement limitation, joint failure, and ultimately disability and joint replacement. OA constitutes a major challenge for the health systems and affects 242 million people globally. Moreover, OA is highly prevalent in Europe with an estimated 19.7-42.3% in the elderly population. MIRACLE concept is to access the biochemical on articular cartilage, which precedes OA. The feasibility of this approach as a diagnostic method has been demonstrated by MIRACLE consortium (TRL4). MIRACLE has also prototyped a MIR-probe with potential use for diagnostics (TRL4). By technology development reaching TRL 6-7, MIRACLE will bring to the arthroscopy market the first MIR-based probe providing an unique, accurate and quantitative diagnostic tool for the orthopedic surgeon. This will be achieved combining three novel photonics components: (i) a quantum cascade laser array tailored to biodiagnostics, (ii) an on-chip beam combiner for efficient radiation coupling, and (iii) MIR sensing probe for imaging. These components will be integrated in a medical device to be placed in the arthroscopy market (valued at $4 billion in 2015). In addition to add value to the European medical equipment industry, MIRACLE strives towards cost reduction of OA patients (currently costs/patient/year €10,452) contributing to more affordable public health care and promoting wellbeing in the European ageing population.