The SOMA project tackles three grand challenges in the field of upper-limb neuroprosthetics: a) to develop a completely novel low invasive peripheral interface for restoring natural and multimodal tactile sensations in amputee subjects, with high selectivity and discrimination capabilities thanks to focused UltraSound (US) stimulation, b) to develop and validate an in-vitro model of the innervated natural skin and its sensory receptors, through the application of cutting edge tissue engineering technology and neurocomputational modelling, for the study of spatio-temporal relationships between cutaneous stimuli and afferent neural signals, and for the validation of stimulation techniques of the Peripheral Nervous System (PNS), c) to demonstrate the effectiveness of the newly developed interface through the closed-loop sensori-motor control of an upper-limb prosthesis. The new insights obtained with in-vivo experiments revealed that FUS stimulation does not appear to be a reliable and safe method for constituting a suitable nerve interface for use in humans. Still keeping the ultimate goal of developing a novel solution of peripheral interface with reduced invasiveness, a Hybrid US-electrical stimulation system is being investigated, together with the fallback option of a fully implantable and wireless solution for electrical nerve stimulation. Therefore, the SOMA system will rely on focused US probes for decoding motion intention, implantable wireless technologies for feeding sensory information encoded through new algorithms capable of generating multimodal sensations related to mechanoreceptors (for mechanical pressure), nociceptors (for pain) and thermoreceptors (for changes in temperature). The in-vitro model of the somatosensory system will be composed of a biohybrid fully innervated sensitive skin, which replicates in-vitro the complex cutaneous somatosensory system of the human skin. The project aims to experimentally validate the in-vitro model, to unravel the role of the sense of touch in both exteroception and proprioception and to provide as ultimate goal a test-bed useful to investigate and test new stimulation techniques. The development of the novel peripheral interface and the in-vitro model will be carried out in parallel through a comparative analysis with the most advanced state-of-the art stimulation techniques and an experimental validation with in-vivo tests on animal models. Finally, a clinical validation of the SOMA technologies on amputees will be carried out.