Combinando Novas Terapias Celulares e Polímeros Biodegradáveis na Promoção da Regeneração do Nervo Periférico

The aim of the NEUROBIOTECH project is to develop a new NGC based on biopolymers, namely based on hyaluronate, that can be used as a new biomaterial to promote peripheral nerve regeneration after peripheral nerve injuries. This new NGC will be tested both alone or in combination with the already tested and established cell therapy based on OM-MSCs, to allow its future application in clinical practice under the assumptions of the "one health” concept. To this end, the project will initially involve the production and physical and biomechanical characterization of the new NGC. The guide tubes will then be tested in vitro to determine their cytocompatibility and absence of toxicity over OM-MSCs. Before their application in pre-clinical trials, the NGCs will also be tested in vivo for their biocompatibility, by being applied subcutaneously in the rat model to evaluate the local and systemic effects after implantation, following the assumptions of ISO 10993-6 :2016. Once in vitro and in vivo safety is determined, NGCs will be used in the rat model, a well-established, rapid, safe and reliable model, and also in the sheep model, a complex animal model that allows more effectively to mimic naturally occurring injuries in human and veterinary patients. In both cases, size-adapted guide tubes will be applied after induction of neurotmesis injuries, both alone and in combination with OM-MSCs and their secretion products, and the animals will be subjected to functional, ultrasound, electromyographic and kinematic assessments to determine of functional recovery, and the intervened nerves and effector muscles will be harvested for histomorphometric and stereological evaluation. In this way, a complete characterization of the effects of the new therapeutic combination considered in a multidimensional way will be achieved, allowing to guarantee its safety, ease of application, repeatability, and effective efficacy both in functional recovery and in inducing histological and ultrastructural reorganization of the tissues influenced by pro-regenerative therapy. Finally, and based on the results obtained in the animal model, it will be considered to start a pilot clinical trial with a limited number of companion animals diagnosed with peripheral nerve injury, in order to introduce and test the developed therapeutic combination in veterinary clinical practice. The NEUROBIOTECH project is as a multidisciplinary cooperation in which Cellular and Molecular Biology, Biophysics, Biomedicine, Veterinary Medicine and Bioentrepreneurship join efforts to ensure key advances in regenerative medicine in general, and in peripheral nerve regeneration in particular. In addition to creating and making available a new and innovative cell-based therapy involving the use of biomaterials in Veterinary and Human Medicine, the NEUROBIOTECH project will also aim to create a possible new tissue engineering product with commercial potential, always based on the best scientific practices outlined by the European Medicines Agency.