All the planned scientific activities were fully implemented within the end of the project by each ESR, considering both the design of the whole project in general and the specific projects of each ESR.
Materials currently used for musculoskeletal regeneration and prosthesis manufacturing, including metals and ceramics, were produced, deeply characterised concerning physicochemical properties, such as surface and bulk chemical composition, morphology, structure, release kinetics of doped ions, surface charge and degradation rates when relevant; they have also been modified in order to add specific functionalities. The new materials so developed were assessed regarding biocompatibility, and their efficacy for promoting musculoskeletal regeneration or for preventing negative condition affecting this latter, including infection, was carefully studied as well. Moreover, some materials and/or patient-related risk profiles were identified: they include the composition of the glycosome of the extracellular matrix of intervertebral disks disease and the amount and content of extracellular vesicles coming from human primary mesenchymal stem cells or immune -cells when in contact with materials with different composition or surface texture. The perfusion and sonographic techniques to cultivate cells in 3D condition were also optimised, and specific devices for seeding and cultivation of cells were optimised and validated. Several 3D advanced cell models were developed to study the cell/stress responses, the immune-modulation role of extracellular matrix including proteins and glycans, vascularisation, innervation and immune systems in musculoskeletal tissues regeneration with or without biomaterials and to screen drugs for osteosarcoma treatment. Lab-on-chip devices were designed to cultivate and analyse some of these models. Digital simulations of degradation and active agents release from materials were set. Algorithms to describe the generation of extracellular vesicle from mesenchymal stem cell and immune cells were set. Machine-learning algorithms using available clinical data sets will be developed to serve as decision supporting systems.
At the same time, a strong effort was put by ESRs and their supervisors in ensuring a wide dissemination of achieved results, delivering 49 articles in peer-reviewed scientific journals and 60 presentations (27 oral presentations and 33 posters) at international conferences. A proper exploitation strategy for each of the identified Exploitable Results was also defined, including the activities to be implemented beyond the project end.
