Post-traumatic anosmia is a common clinical condition referring to the complete loss of the sense of smell secondary to traumatic brain injury. During brain trauma, the relative movement of the brain to the skull shears the axons of the olfactory sensory neurons at the level of the cribriform plate in the anterior skull base. Post-traumatic inflammation at this level may induce scar tissue formation creating a barrier for new olfactory axons to grow from the olfactory mucosa in the nose towards the centrally located olfactory bulb. Only about 15% of affected patients experience some degree of recovery, whereas the majority suffer from several negative and permanent consequences ranging from diminished food enjoyment to the inability to detect potential hazards such as gas leaks or spoiled food. For some professionals, such as cooks or firefighters, anosmia may lead to an inability to work. Today, there is no cure, making post-traumatic anosmia a true unmet clinical need. In the normally functioning olfactory system, airborne odour molecules are carried into the nasal cavity where they activate specific neuronal olfactory receptors located in the olfactory epithelium. These olfactory neurons undergo continuous and life-long renewal from a pool of tissue-resident neuroprogenitors. During development, they project axons through the cribriform plate bone towards the olfactory bulb. The hereby presented project aims at recapitulating this concept in post-traumatic anosmia and to re-establish axonal connection between progenitor-derived olfactory neurons in the olfactory mucosa and the centrally located bulb. To overcome the scar tissue, a functionalized biomaterial is implanted at the level of the cribriform plate to open a new passage and to induce guided growth along a scaffold towards the olfactory bulb. On the way to achieve this ambitious goal, intermediate goals had to be met first within this project. First, in vitro culture conditions for olfactory neurons were successfully optimized and the results published. Second, guided growth of murine and human olfactory neurons was induced on custom-made biomaterials in vitro in 3D. Third, a mouse model for post-traumatic anosmia was created in the laboratory including a surgical approach to safely implant the biomaterial and a new behavioral test for the murine olfactory function. Finally, the overall concept of olfactory regeneration in mice with post-traumatic anosmia was assessed in a sham-controlled trial in vivo. Following post-traumatic anosmia, animals implanted with the biomaterial to induce regrowth of olfactory neurons recovered the smell function, whereas non-implanted animals did not. These encouraging functional results still lack the histological proof of axonal regeneration as the cause for recovery and must be considered still preliminary. In conclusion the concept of guided regrowth of olfactory sensory neurons through implanted biomaterials is worth to be pursued beyond the scope of the current thesis with the goal to develop a cure for patients suffering from post-traumatic smell loss in the future.