Graphene oxide scaffolds promote functional improvements mediated by scaffold-invading axons in thoracic transected rats

Millions of patients and their caretakers live and deal with the devastating consequences of spinal cord injury (SCI) worldwide. Despite outstanding advances in the field to both understand and tackle these pathologies, a cure for SCI patients, with their peculiar characteristics, is still a mirage....

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Main Authors: Marta Zaforas, Esther Benayas, Raquel Madroñero-Mariscal, Ana Domínguez-Bajo, Elena Fernández-López, Yasmina Hernández-Martín, Ankor González-Mayorga, Elena Alonso-Calviño, Eduardo R. Hernández, Elisa López-Dolado, Juliana M. Rosa, Juan Aguilar, María C. Serrano
Format: Article
Language:English
Published: KeAi Communications Co., Ltd. 2025-05-01
Series:Bioactive Materials
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Online Access:http://www.sciencedirect.com/science/article/pii/S2452199X24005681
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author Marta Zaforas
Esther Benayas
Raquel Madroñero-Mariscal
Ana Domínguez-Bajo
Elena Fernández-López
Yasmina Hernández-Martín
Ankor González-Mayorga
Elena Alonso-Calviño
Eduardo R. Hernández
Elisa López-Dolado
Juliana M. Rosa
Juan Aguilar
María C. Serrano
author_facet Marta Zaforas
Esther Benayas
Raquel Madroñero-Mariscal
Ana Domínguez-Bajo
Elena Fernández-López
Yasmina Hernández-Martín
Ankor González-Mayorga
Elena Alonso-Calviño
Eduardo R. Hernández
Elisa López-Dolado
Juliana M. Rosa
Juan Aguilar
María C. Serrano
author_sort Marta Zaforas
collection DOAJ
description Millions of patients and their caretakers live and deal with the devastating consequences of spinal cord injury (SCI) worldwide. Despite outstanding advances in the field to both understand and tackle these pathologies, a cure for SCI patients, with their peculiar characteristics, is still a mirage. One of the most promising therapeutic strategies to date for these patients involves the use of epidural electrical stimulation. In this context, electrically active materials such as graphene and its derivates become particularly interesting. Indeed, solid evidence of their capacity to closely interact with neural cells and networks is growing. Encouraged by previous findings in our laboratory on the exploration of 3D porous reduced graphene oxide (rGO) scaffolds in chronic cervical hemisected rats (C6), herein we report their neuro-reparative properties when chronically implanted in complete transected rats (T9-T10), in which no preserved contralateral neural networks can assist in any observed recovery. Electrophysiological recordings from brainstem regions show antidromic activation of a small population of neurons in response to electrical stimulation caudal to the injury. These neurons are located in the Gigantocellular nucleus of reticular formation and vestibular nuclei, both regions directly related to motor functions. Together with histological features at the lesion site, such as more abundant and larger blood vessels and more abundant, longer and more homogeneously distributed axons, our results corroborate that rGO scaffolds create a permissive environment that allows the invasion of functional axonic processes from neurons located in brainstem nuclei with motor function in a rat model of complete thoracic transection. Additionally, behavioral tests evidence that these scaffolds play an important role in whole-body mechanical stabilization (postural control) proved by the absence of scoliosis, a higher trunk stability and a larger cervico-thoraco-lumbar movement range in rGO-implanted rats.
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spelling doaj-art-367c4833bc8040468d6e2189de0889e72025-01-12T05:25:33ZengKeAi Communications Co., Ltd.Bioactive Materials2452-199X2025-05-01473250Graphene oxide scaffolds promote functional improvements mediated by scaffold-invading axons in thoracic transected ratsMarta Zaforas0Esther Benayas1Raquel Madroñero-Mariscal2Ana Domínguez-Bajo3Elena Fernández-López4Yasmina Hernández-Martín5Ankor González-Mayorga6Elena Alonso-Calviño7Eduardo R. Hernández8Elisa López-Dolado9Juliana M. Rosa10Juan Aguilar11María C. Serrano12Laboratorio de Neurofisiología Experimental, Hospital Nacional de Parapléjicos, Finca La Peraleda s/n, 45071, Toledo, SpainInstituto de Ciencia de Materiales de Madrid (ICMM), Consejo Superior de Investigaciones Científicas (CSIC), Calle Sor Juana Inés de la Cruz 3, 28049, Madrid, SpainLaboratory of Interfaces for Neural Repair, Hospital Nacional de Parapléjicos, SESCAM, Finca La Peraleda s/n, 45071, Toledo, Spain; Instituto de Investigación Sanitaria de Castilla-La Mancha (IDISCAM), SpainInstituto de Ciencia de Materiales de Madrid (ICMM), Consejo Superior de Investigaciones Científicas (CSIC), Calle Sor Juana Inés de la Cruz 3, 28049, Madrid, SpainLaboratorio de Neurofisiología Experimental, Hospital Nacional de Parapléjicos, Finca La Peraleda s/n, 45071, Toledo, Spain; Instituto de Investigación Sanitaria de Castilla-La Mancha (IDISCAM), SpainLaboratory of Interfaces for Neural Repair, Hospital Nacional de Parapléjicos, SESCAM, Finca La Peraleda s/n, 45071, Toledo, Spain; Instituto de Investigación Sanitaria de Castilla-La Mancha (IDISCAM), SpainLaboratory of Interfaces for Neural Repair, Hospital Nacional de Parapléjicos, SESCAM, Finca La Peraleda s/n, 45071, Toledo, SpainLaboratorio de Neurofisiología Experimental, Hospital Nacional de Parapléjicos, Finca La Peraleda s/n, 45071, Toledo, Spain; Instituto de Investigación Sanitaria de Castilla-La Mancha (IDISCAM), SpainInstituto de Ciencia de Materiales de Madrid (ICMM), Consejo Superior de Investigaciones Científicas (CSIC), Calle Sor Juana Inés de la Cruz 3, 28049, Madrid, SpainLaboratory of Interfaces for Neural Repair, Hospital Nacional de Parapléjicos, SESCAM, Finca La Peraleda s/n, 45071, Toledo, Spain; Design and development of biomaterials for neural regeneration, HNP, Associated Unit to CSIC through ICMM, Finca La Peraleda s/n, 45071, Toledo, Spain; Instituto de Investigación Sanitaria de Castilla-La Mancha (IDISCAM), SpainDesign and development of biomaterials for neural regeneration, HNP, Associated Unit to CSIC through ICMM, Finca La Peraleda s/n, 45071, Toledo, Spain; Neuronal Circuits and Behaviour Group, Hospital Nacional de Parapléjicos, 45071, Toledo, Spain; Instituto de Investigación Sanitaria de Castilla-La Mancha (IDISCAM), SpainLaboratorio de Neurofisiología Experimental, Hospital Nacional de Parapléjicos, Finca La Peraleda s/n, 45071, Toledo, Spain; Design and development of biomaterials for neural regeneration, HNP, Associated Unit to CSIC through ICMM, Finca La Peraleda s/n, 45071, Toledo, Spain; Instituto de Investigación Sanitaria de Castilla-La Mancha (IDISCAM), Spain; Corresponding author. Laboratorio de Neurofisiología Experimental, Hospital Nacional de Parapléjicos, Finca La Peraleda s/n, 45071, Toledo, Spain.Instituto de Ciencia de Materiales de Madrid (ICMM), Consejo Superior de Investigaciones Científicas (CSIC), Calle Sor Juana Inés de la Cruz 3, 28049, Madrid, Spain; Corresponding author. Instituto de Ciencia de Materiales de Madrid (ICMM), Consejo Superior de Investigaciones Científicas (CSIC), Calle Sor Juana Inés de la Cruz 3, 28049, Madrid, Spain.Millions of patients and their caretakers live and deal with the devastating consequences of spinal cord injury (SCI) worldwide. Despite outstanding advances in the field to both understand and tackle these pathologies, a cure for SCI patients, with their peculiar characteristics, is still a mirage. One of the most promising therapeutic strategies to date for these patients involves the use of epidural electrical stimulation. In this context, electrically active materials such as graphene and its derivates become particularly interesting. Indeed, solid evidence of their capacity to closely interact with neural cells and networks is growing. Encouraged by previous findings in our laboratory on the exploration of 3D porous reduced graphene oxide (rGO) scaffolds in chronic cervical hemisected rats (C6), herein we report their neuro-reparative properties when chronically implanted in complete transected rats (T9-T10), in which no preserved contralateral neural networks can assist in any observed recovery. Electrophysiological recordings from brainstem regions show antidromic activation of a small population of neurons in response to electrical stimulation caudal to the injury. These neurons are located in the Gigantocellular nucleus of reticular formation and vestibular nuclei, both regions directly related to motor functions. Together with histological features at the lesion site, such as more abundant and larger blood vessels and more abundant, longer and more homogeneously distributed axons, our results corroborate that rGO scaffolds create a permissive environment that allows the invasion of functional axonic processes from neurons located in brainstem nuclei with motor function in a rat model of complete thoracic transection. Additionally, behavioral tests evidence that these scaffolds play an important role in whole-body mechanical stabilization (postural control) proved by the absence of scoliosis, a higher trunk stability and a larger cervico-thoraco-lumbar movement range in rGO-implanted rats.http://www.sciencedirect.com/science/article/pii/S2452199X24005681Complete thoracic transectionElectrophysiological recordingGraphene oxideNeural tissue engineeringScaffold
spellingShingle Marta Zaforas
Esther Benayas
Raquel Madroñero-Mariscal
Ana Domínguez-Bajo
Elena Fernández-López
Yasmina Hernández-Martín
Ankor González-Mayorga
Elena Alonso-Calviño
Eduardo R. Hernández
Elisa López-Dolado
Juliana M. Rosa
Juan Aguilar
María C. Serrano
Graphene oxide scaffolds promote functional improvements mediated by scaffold-invading axons in thoracic transected rats
Bioactive Materials
Complete thoracic transection
Electrophysiological recording
Graphene oxide
Neural tissue engineering
Scaffold
title Graphene oxide scaffolds promote functional improvements mediated by scaffold-invading axons in thoracic transected rats
title_full Graphene oxide scaffolds promote functional improvements mediated by scaffold-invading axons in thoracic transected rats
title_fullStr Graphene oxide scaffolds promote functional improvements mediated by scaffold-invading axons in thoracic transected rats
title_full_unstemmed Graphene oxide scaffolds promote functional improvements mediated by scaffold-invading axons in thoracic transected rats
title_short Graphene oxide scaffolds promote functional improvements mediated by scaffold-invading axons in thoracic transected rats
title_sort graphene oxide scaffolds promote functional improvements mediated by scaffold invading axons in thoracic transected rats
topic Complete thoracic transection
Electrophysiological recording
Graphene oxide
Neural tissue engineering
Scaffold
url http://www.sciencedirect.com/science/article/pii/S2452199X24005681
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