Anagrafe della ricerca

The ambition of the BIGMECH project is to build a pioneering knowledge-generation framework unravelling for the first time the cell-scale signaling pathways and the tissue-scale effects induced in bone tissue by native-like physical stimuli combined with PEMF stimulation. For this purpose, the main technological aim will be the optimization of a novel biomimetic investigation platform, based on a smart bioreactor system and 3D scaffold-based bone tissue models. In detail, a perfusion bioreactor will be upgraded for enabling in vitro adaptive dynamic culture of 3D constructs under tunable and combinable physical stimuli (shear stress, intermittent pressure, PEMF stimulation) and real-time monitored conditions. Unique 3D-printed scaffolds, mimicking the complex bone microarchitecture, will be developed and, seeded with mesenchymal stem cells, will be cultured within the bioreactor for developing reliable 3D bone tissue models. The biomimetic platform will then be used for applying native-like physical stimuli without and with PEMF stimulation on the 3D bone tissue models. High throughput transcriptomics will reveal intracellular signaling events triggered by the imposed physical stimuli. Transcriptomic data will be treated by high performance machine learning (ML) tools for decrypting complex networks and for extracting the relationships between gene expression and applied physical stimuli. As main scientific result, a novel mechanotransduction Knowledge Base will be released as open and free database. The combination of the pioneering biomimetic investigation platform, cutting-edge high throughput screening, and high performance ML tools will enable reaching a thorough understanding of the correlations between applied biophysical stimuli and biological response, with the final aim to define the rationale basis for improved biophysical stimulation treatments, in view of precision orthopedic medicine.