[EN] Spinal cord injury (SCI) continues to be a therapeutic challenge as there is no cure to date. Thus, the implementation of novel implantable devices that could be placed at the injured tissue has been widely explored by researchers working in different areas of Tissue Engineering and Materials Science and clinicians. In this thesis, we have investigated two different substrates as potentially efficient neural interfaces based on different strategies. On the one hand, we tested the in vitro biocompatibility of 2D metal-based nanowires (NWs) that could work as nanoelectrodes. These NWs will be eventually included in a device able of acting as a bypass once placed at the lesion site after SCI. On the other hand, two kinds of biocompatible 3D scaffolds made of reduced graphene oxide (rGO) were chronically implanted in the right hemisected cervical spinal cord (C6 level) of a rat experimental model of SCI. In vivo biocompatibility, in terms of behavior affectation along with systemic and local tissue responses, was thoroughly studied four months after implantation following an interdisciplinary approach. The results obtained in this thesis demonstrate the promising potential of both NWs and rGO scaffolds as neural interfaces capable of fostering the repair of the injured spinal cord. Further studies including biological functionalization and the application of rehabilitation protocols, such as aerobic motor training, might improve their therapeutic potential by a synergistic effect of topographical, chemical, mechanical and sensory stimuli, thus boosting neural repair after SCI.

[ES] Actualmente no existe ningún tratamiento eficaz para la lesión medular, caracterizada principalmente por el daño de los axones neuronales y la creación de un entorno inhibitorio para la regeneración. En esta tesis, hemos investigado dos plataformas diferentes capaces de actuar como interfaces neurales. Por un lado, hemos estudiado la biocompatibilidad in vitro de nanohilos metálicos que funcionarán como nanoelectrodos dentro de un dispositivo capaz de actuar como “bypass” en la lesión. Estos nanohilos metálicos se han fabricado por electrodeposición de níquel (Ni) u oro (Au) sobre una base plana y flexible de Au, dispuestos verticalmente sobre ella. Por otro lado, dos tipos de plataformas 3D fabricadas a partir de óxido de grafeno reducido se han implantado crónicamente en un modelo de hemisección de la médula espinal cervical en rata. Los implantes han consistido en una espuma altamente porosa y microfibras integradas en un hidrogel de gelatina. Con respecto a los electrodos metálicos, la composición química y la nanotopografía modulan el comportamiento de las células neurales in vitro. Con respecto a los biomateriales de grafeno, ambos implantes han promovido la estabilización del tejido espinal lesionado, así como la presencia de estructuras neuronales acompañadas de vasos sanguíneos en la lesión. Además, las espumas de grafeno reducen el daño perilesional y no causan efectos adversos por compresión ni tracción. En conclusión, estos resultados demuestran el potencial de estas plataformas como interfaces neurales para la reparación de la médula espinal lesionada.

This thesis project has been made partially possible thanks to the financial support received from the European Union´s Horizon 2020 research and innovation programme under grant agreement No. 737116 corresponding to the ByAxon project (H2020-FET-OPEN-RIA, EC; 2017-2020).

Peer reviewed