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Precision medicine for muscoloskeletal regeneration, prosthetics and active ageing

Periodic Reporting for period 1 - PREMUROSA (Precision medicine for muscoloskeletal regeneration, prosthetics and active ageing)

Période du rapport: 2020-01-01 au 2021-12-31

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. Personalized medicine has evolved as a model aiming to transform translational research into a patient-specific (“precise”) concept, which incorporates tailored diagnostic measures and customized targeted therapies, improving the clinical success rate. This approach is currently applied in some medical fields such as Oncology. However, it but it has received poor attention in orthopedics where the concept of “personalization” 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 andthe 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-centered 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.
The planned scientific activities within the first two years of the project implementation have been carried out by each ESR considering 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, have been produced, characterized 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. All the elements above have been finely studied and validated, thus they can now be used to obtain reproducible results. The interaction of the materials with proteins and mesenchymal stem cells was also assessed. The effect of dynamic conditions during cell seeding onto scaffolds was studied and optimized with different approaches, including perfusion and sonographic techniques.
Moreover, several 3D advanced cell models were developed to study the cell/stress responses, the role of extracellular matrix including proteins and glycans, vascularization, innervation and immune systems in musculoskeletal tissues regeneration with or without biomaterials. Preliminary digital simulations were set.
At the same time, ESRs have started publishing their work in scientific articles, reaching a total of 11 articles published as co-authors by December 2021.
PREMUROSA is addressing key societal challenges and its results are very promising with respect to the achievement significant progresses beyond the state of the art and significant impacts, which include:
a) the optimization 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 and the consequent reduction of the recurrence to animal experimentation;
c) the optimization 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 is also training a cohort of 13 young scientists addressing multidisciplinary scientific skill, as well as transversal skills such as entrepreneurship and European collaborative spirit.
The first PREMUROSA social dinner with the ESRs in Porto
Map of the PREMUROSA Consortium