The musculoskeletal system is extremely vulnerable to ageing and traumatic events, and common clinical conditions often exert a high burden on the clinical system. For patients requiring bone-substitute implants to treat critical-size bone defects, new solutions are required for meeting important unmet needs: personalised solutions for better clinical outcomes; improvements in materials to ensure higher mechanical reliability without compromising bioactive and bioresorbable properties; optimised manufacturing technologies for materials and products of high reliability and quality. REBONE is a four-year doctoral network that aims to innovatively train a new generation of researchers to develop a multidisciplinary optimisation process to provide technologies for 3D-printed personalised bone replacement implants based on bioactive ceramics. The ultimate scientific goal is to construct a platform of computational tools that will enable clinical experts to produce customized bone graft substitutes for the treatment of critical-size bone defects. This innovation will ensure that an ideal treatment solution is found on a patient-specific basis in terms of: i) mechanical and mechano-biological performance, ii) surgical implantability, and iii) manufacturing process reliability. Furthermore REBONE will develop state-of-the-art in silico models based on advanced computational methods and advanced characterisation and validation techniques to obtain personalised implants with a surgical planning visualization system in mixed reality with the following characteristics: i) tailored and reliable mechanical and physical properties; ii) best osteointegration capability; iii) targeted mechanical, physical and mechano-biological functions with patient-specific constraints taking into account the load-bearing anatomical location. Four selected clinical cases will be used as demonstrators of the optimization design and manufacturing process.