Periodic Reporting for period 2 - PREMUROSA (Precision medicine for muscoloskeletal regeneration, prosthetics and active ageing)
Periodo di rendicontazione: 2022-01-01 al 2024-09-30
Musculoskeletal diseases are reported to affect roughly half of the world’s population over 60, strongly impacting the quality of life. They are a significant burden on individuals, healthcare and welfare systems, with huge direct and indirect costs. The treatment of musculoskeletal disorders is often based either on prosthetic rehabilitation or regenerative surgical procedures, including scaffold implantation. In both cases, individual tissue healing and regeneration response, and the appropriateness of the implanted device, markedly affect the outcome. Personalised medicine has evolved as a model aiming to transform translational research into a patient-specific (“precise”) concept, which incorporates tailored diagnostic measures and customised targeted therapies, improving the clinical success rate. This approach is currently applied in some medical fields such as Oncology. However, it has received poor attention in orthopaedics where the concept of “personalisation” is still mostly limited to a mere adaptation of the device geometry to the patient anatomy without considering any patient-specific capability in tissue regeneration. In addition, despite the significant improvement in developing multi-functional smart biomaterials and medical devices for tissue regeneration by classical “design and engineering” approaches, the pre-clinical models for the biological assessment of their efficacy have not followed the same evolution. Because of that, no more than one-third of innovations are translated to clinical practice. The complexity of the regenerative process and the difficulty in predicting and controlling the interaction between tissue and biomaterial and the lack of reliable and rapid execution preclinical models addressed to predict the clinical performances are certainly responsible for these gaps. The aim of PREMUROSA (Precision medicine for musculoskeletal regeneration, prosthetics, and active ageing) is thus to help precise patient-centred application of regenerative treatments by developing new in-vitro tests and decision support systems (DSS), while training 13 young scientists (ESRs) with multidisciplinary approach and interaction.
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.
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.
PREMUROSA addressed key societal challenges and its results are very promising with respect to the achievement of significant progresses beyond the state of the art and significant impacts, which include: a) the optimisation of clinical choices and the consequent improvement of quality of life of the patients and the reduction of healthcare system costs; b) the development of new assays for materials pre-clinical screening to speed up technology discovery and safety/efficacy assessment while reducing the recurrence to animal experimentation; c) the optimisation of the existing devices and the development of the new products (devices and digital tools) and the consequent strengthening of the industrial competitiveness and definitively of employment in the industrial health sector. PREMUROSA also trained a cohort of 13 young scientists addressing multidisciplinary scientific skill, as well as transversal skills such as entrepreneurship and European collaborative spirit.