Study design Cohort study of patients with spinal cord injury (SCI). Objectives To describe the clinical and analytical features of a coronavirus disease 2019 (Covid-19) infected cohort with SCI to enable accurate diagnosis and to outline prevention measures. Setting This study was conducted at the National Hospital for Paraplegics (Toledo, Spain). Methods A cohort analysis of seven patients with SCI infected by Covid-19 was performed. Diagnosis was confirmed with reverse transcriptase polymerase chain reaction (RT-PCR) of nasal exudate or sputum samples. Clinical, analytical, and radiographic findings were registered.Results RT-PCR detected COVID-19 infection in all patients, affecting males and people with a cervical level of injury more often (five out of seven). The average delay for diagnostic confirmation was 4 days (interquartile range, 1-10). Fever was the most frequent symptom (six out of seven). The second most common symptom was asthenia (four out of seven), followed by dyspnea, cough, and expectoration (three out of seven for each symptom). The Modified Early Warning System score for Covid-19 severity rating was classified as severe in five out of seven cases. All but one patient showed radiological alterations evident in chest X-rays at the time of diagnosis. All patients recovered gradually. Conclusion Our patients with SCI and Covid-19 infection exhibited fewer symptoms than the general population. Furthermore, they presented similar or greater clinical severity. The clinical evolution was not as pronounced as had been expected. This study recommends close supervision of the SCI population to detect early compatible signs and symptoms of Covid-19 infection.

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Neural tissue engineering approaches show increasing promise for the treatment of neural diseases including spinal cord injury, for which an efficient therapy is still missing. Encouraged by both positive findings on the interaction of carbon nanomaterials such as graphene with neural components and the necessity of more efficient guidance structures for neural repair, we herein study the potential of reduced graphene oxide (rGO) microfibers as substrates for neural growth in the injured central neural tissue. Compact, bendable, and conductive fibers are obtained. When coated with neural adhesive molecules (poly-l-lysine and N-cadherin), these microfibers behave as supportive substrates of highly interconnected cultures composed of neurons and glial cells for up to 21 days. Synaptic contacts close to rGO are identified. Interestingly, the colonization by meningeal fibroblasts is dramatically hindered by N-cadherin coating. Finally, in vivo studies reveal the feasible implantation of these rGO microfibers as a guidance platform in the injured rat spinal cord, without evident signs of subacute local toxicity. These positive findings boost further investigation at longer implantation times to prove the utility of these substrates as components of advanced therapies for enhancing repair in the damaged central neural tissue including the injured spinal cord.

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Understanding neural physiopathology requires advances in nanotechnology‐based interfaces, engineered to monitor the functional state of mammalian nervous cells. Such interfaces typically contain nanometer‐size features for stimulation and recording as in cell‐non‐invasive extracellular microelectrode arrays. In such devices, it turns crucial to understand specific interactions of neural cells with physicochemical features of electrodes, which could be designed to optimize performance. Herein, versatile flexible nanostructured electrodes covered by arrays of metallic nanowires are fabricated and used to investigate the role of chemical composition and nanotopography on rat brain cells in vitro. By using Au and Ni as exemplary materials, nanostructure and chemical composition are demonstrated to play major roles in the interaction of neural cells with electrodes. Nanostructured devices are interfaced to rat embryonic cortical cells and postnatal hippocampal neurons forming synaptic circuits. It is shown that Au‐based electrodes behave similarly to controls. Contrarily, Ni‐based nanostructured electrodes increase cell survival, boost neuronal differentiation, and reduce glial cells with respect to flat counterparts. Nonetheless, Au‐based electrodes perform superiorly compared to Ni‐based ones. Under electrical stimulation, Au‐based nanostructured substrates evoke intracellular calcium dynamics compatible with neural networks activation. These studies highlight the opportunity for these electrodes to excite a silent neural network by direct neuronal membranes depolarization.

Spinal cord injury (SCI) is characterized by the disruption of neuronal axons and the creation of an inhibitory environment for spinal tissue regeneration. For decades, researchers and clinicians have been devoting a great effort to develop novel therapeutic approaches which include the fabrication of biocompatible implants that could guide neural tissue repair in the lesion site in an attempt to recover the functionality of the nervous tissue. In this context, although fiberlike structures have been hypothesized to serve as a topographical guidance for axonal regrowth, work on the exploration of this type of materials is still limited for SCI. Aiming to develop such guidance platforms, we recently designed and explored in vitro reduced graphene oxide materials in the shape of microfibers (rGO-MFs). After preliminary studies to assess the feasibility of their implantation at the injured spinal cord in vivo, no evident signs of subacute local toxicity were noticed (10 days of implantation). In this work, we specifically examine for the first time the regenerative potential of these scaffolds, slightly modified in their fabrication for improved reproducibility, when chronically interfaced with a cervical spinal cord injury. After extensive characterization of their physicochemical properties and in vitro experiments with neural progenitor cells, their neural regenerative capacity in vivo is investigated in a rat experimental model of SCI after 4 months of implantation (chronic state). Behavioral tests involving the use of forelimbs are performed. Immunofluorescence studies evidence that rGO-MFs scaffolds foster the presence of neuronal structures along with blood vessels both within the epicenter and in the surroundings of the lesion area. Moreover, the inflammatory response does not worsen by the presence of this material. These findings outline the potential of rGO-MF-based scaffolds to promote regenerative features at the injured spinal cord such as axonal and vascular growth. Further studies including biological functionalization might improve their therapeutic potential by a synergistic effect of topographical and chemical cues, thus boosting neural repair after SCI.

The attractiveness of graphene-derived materials (GDMs) for neural applications has fueled their exploration as components of biomaterial interfaces contacting the brain and the spinal cord. In the last years, an increasing body of work has been published on the ability of these materials to create biocompatible and biofunctional substrates able to promote the growth and activity of neural cells in vitro and positively interact with neural tissues when implanted in vivo. Encouraging results in the central nervous tissue might impulse the study of GDMs towards preclinical arena. In this mini-review article, we revise the most relevant literature on the interaction of GDMs with the spinal cord. Studies involving the implantation of these materials in vivo in the injured spinal cord are first discussed, followed by models with spinal cord slides ex vivo and a final description of selected results with neural cells in vitro. A closing debate of the major conclusions of these results is presented to boost the investigation of GDMs in the field.

Study design: Cohort study of patients with spinal cord injury (SCI)Objectives: To describe the clinical and analytical features of a Covid-19 infected cohort with SCI to contribute new knowledge for a more accurate diagnosis and to outline prevention measures.Setting: This study was conducted at the National Hospital for Paraplegics (Toledo, Spain).Methods: A cohort analysis of seven patients with SCI infected by Covid-19 was carried out. Diagnosis was confirmed with reverse transcriptase polymerase chain reaction (RT-PCR) of nasal exudate or sputum samples. Clinical, analytical and radiographic findings were registered.Results: RT-PCR detected COVID-19 infection in all patients, affecting males and people with a cervical level of injury more often (5 out 7). The average delay for diagnostic confirmation was 4 days (interquartile range, 1-10). Fever was the most frequent symptom (6 out of 7). The second most common symptom was asthenia (4 out of 7), followed by dyspnea, cough and expectoration (3 out of 7 for each symptom). The MEWS score for Covid-19 severity rating was classified as severe in 5 out of 7. All but one patient showed radiological alterations evident in chest X-Rays at the time of diagnosis. All patients recovered gradually.