Piezo4Spine aims to develop a novel multifactorial therapy for spinal cord injury (SCI) conceived as a disruptive platform enabling unprecedented multiscale actuation to drive functional neural repair by more accurately tackling SCI complexity. It originally relies on the pivotal role that mechanotransduction plays in the physiology and physiopathology of tissue and organ functions, never explored before for SCI. We will develop a 3D bioprinted mesh containing nanocarriers with therapeutic agents acting at two pivotal aspects of neural repair: mechanotransduction and inhibitory scarring using gene therapy strategies. Bioactive nanocarriers will base on cutting-edge nanoparticles whose release will be electrically triggered on-demand via wireless powering. Such 3D-theramesh offers a novel and exceptionally robust biomaterial for delivering agents at the lesion, controlling time and dose. Current advances on SCI therapies focus on rehabilitation, cell transplantation, drugs, biomaterials, and/or electrical stimulation. Although leading to partial sensory/motor recovery, chronic functional deficits limit daily living activities and shorten live expectancy in SCI patients, as they fail to promote successful axon regeneration at the lesion and awake lost functions. By a multidisciplinary consortium combining scientific, technological, clinical and industrial partners enriched by their interdisciplinarity, we envision to overcome limitations of current technologies by tackling multiple cellular targets involved in neural regeneration after SCI with a balanced combination of therapeutic interventions able to optimally promote functional recovery. These radical science-to-technology breakthroughs could enable, if successful, novel technologies and therapies for SCI and many other neural and non-neural pathologies in which some, but not necessarily all, of these targets are involved. Piezo4Spine is funded by the European Union (Horizon Europe Pathfinder)

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