Degeneration of cartilage is a major cause of chronic pain, lost mobility and reduced quality of life for millions of European citizens. From a clinical point of view treatment to achieve cartilage regeneration (hyaline) and not only repair (fibrous) remains a great challenge. No clinical therapy is available that leads to healing of cartilage defects.Current cartilage implants cannot establish the hierarchical tissue organisation that appears critical for normal cartilage function. We hypothesise that a biomimetic zonal organisation is critical for implants to achieve cartilage regeneration.HydroZONES represents an interdisciplinary consortium that adopts a strategy to regenerate, rather than repair, articular cartilage based on the tissues zonal structure and function.HydroZONES will use advanced bioprinting technology for fabrication of 3D biofunctional hydrogel constructs, eventually mechanically reinforced by degradable polymer scaffolds, as biomimetic reconstitution of the zonal organisation of natural cartilage. Constructs will be optimized for cell-free application and also for combination with chrondrogenic cells (chondrocytes and/or MSC). Stringent in vitro and long term in vivo testing of the constructs will be employed that will yield a new clinical standard for pre-clinical testing.Cutting edge 3D tissue models and bioreactor technology will be used together with in silico modelling to develop a predictive in vitro assay and test system that will be validated against the in vivo data.Installation of a quality and regulatory affair management system, GMP production, accredited in vitro testing and involvement of clinical partners and companies with experience in clinical trials ensures that the best performing construct will be brought into an optimal position for entering clinical trials at project end. HydroZONES will thus advance the European Union as world leader in the field of joint cartilage regeneration.