Osteoarthritis (OA) is a chronic disease involving the degeneration of articular cartilage and subchondral bone. It represents the single most common cause of disability in older adults. Being aging, obesity, trauma and gender risk factors for OA, its societal burden is rapidly rising. Across EU, over 40 million people are affected by OA. Current treatment options aim at modulating the symptoms rather than curing this chronic disease. Consequently, joint replacement continues to be ultimately the sole option. In this context, MEPHOS aims at realizing an integrated strategy for OA treatment based on the intra-articular deposition of hydrogel, polymeric microplates (uPLs) that could simultaneously provide a long-term pharmacological action and mechanical support. To this end, the uPL geometry and mechanical properties will be rationally selected to match the viscoelastic behaviour of cartilage and synovial fluid. Over the course of several weeks, uPLs will sustainably release clinically-approved molecules for pain management and novel small molecules and biologicals; including chemokine and metalloproteinase inhibitors to halt tissue degeneration; glycoproteins, growth factors and stem cell-derived extracellular vesicles to favour tissue regeneration. MEPHOS involves three EU Academic Institutions and a SME for uPL fabrication, and four US Academic Institutions for uPL biological and preclinical characterization. Through interdisciplinary and intersectoral secondments, this project will support the training of EU scientists on sophisticated in-vitro assays and three different preclinical OA models; foster the rational development of uPLs; and instil a translational research culture to bridge preclinical-clinical boundaries. The inclusion of a SME and the Stanford SPARK Translation program documents MEPHOS ambition to develop technologies that could hit the clinic and an industrial market, which is predicted to growth from $1.6 billion in 2016 to $3.5 billion by 2026.