Traumatic Brain Injury (TBI) is the leading cause of disability among young adults in developed countries. TBI can lead to irreversible brain damage and debilitating neurological deficits, especially in severe cases. Few developments have been observed in terms of therapeutic or pharmacological treatments in recent years due to the heterogeneity of lesions which is a complex factor for clinical trials. Current strategies rely mainly on rehabilitation and mechanisms of brain plasticity. These are very limited. As a result, strategies based on cell-based therapies could open the way to new recovery possibilities and lead to a significant reduction in public health costs. Today, simply cell-based strategies have shown their limits: high mortality, low regenerative power. RECOVER is an innovative project aimed at achieving brain repair in a preclinical model of TBI by developing a therapeutic strategy using a combined approach: 1 / cell-based and 2 / based on 3D bio-implants. The project focuses on the repopulation of the lesioned area. In order to replace the extracellular matrix of brain tissue, we have developed an innovative synthetic hydrogel that is suitable for 3D cell culture of neuronal cells. In order to replicate the architectures of the cerebral cortex, an oriented material will be used to guide neuronal cell cultures in 3D. An innovative source of cells is proposed from biopsies of peripheral nerve tissue. It will allow translation into the clinic by autologous transplant. The tissue connections will be studied in vivo in longitudinal optogenetics implemented in MRI (Magnetic Resonance Imaging) during classical functional and in-situ MRI evaluations and at the end of the experiment after sacrifice by histopathological and immunohistochemical analysis of grafted brains. Behavioral tests used for the evaluation of motor function recovery will also be performed. This project is supported by the strong expertise of the candidates on three different and convergent themes: cellular therapy and functional evaluation (ToNIC), hydrogels (IRMCP) and 3D architectures or "scaffolds" (LAAS) thus opening a window opportunity to improve translational research on TBI. The last partner (LabHPEC / ENVT) has the expertise for histopathological assessment of the fate of in situ cell-bioimplants as well as early preclinical safety studies (biocompatibility of materials, local tolerance) of Innovative Drugs and Technologies in a GLP regulatory environment. Beyond TBI, this project is part of a broader research program focusing on neurological disorders following multifactorial brain or spinal cord injury. Indeed, our brain regeneration strategy is applicable to spinal cord injury, brain injury after a stroke, and to damage related to degenerative diseases.