Intravital Assessment of Cells Responses to Conducting Polymer-Coated Carbon Microfibres for Bridging Spinal Cord Injury
The extension of the lesion following spinal cord injury (SCI) poses a major challenge for regenerating axons, which must grow across several centimetres of damaged tissue in the absence of ordered guidance cues. Biofunctionalized electroconducting microfibres (MFs) that provide biochemical signals,...
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MDPI AG
2021-01-01
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author | Bilal El Waly Vincent Escarrat Jimena Perez-Sanchez Jaspreet Kaur Florence Pelletier Jorge Eduardo Collazos-Castro Franck Debarbieux |
author_facet | Bilal El Waly Vincent Escarrat Jimena Perez-Sanchez Jaspreet Kaur Florence Pelletier Jorge Eduardo Collazos-Castro Franck Debarbieux |
author_sort | Bilal El Waly |
collection | DOAJ |
description | The extension of the lesion following spinal cord injury (SCI) poses a major challenge for regenerating axons, which must grow across several centimetres of damaged tissue in the absence of ordered guidance cues. Biofunctionalized electroconducting microfibres (MFs) that provide biochemical signals, as well as electrical and mechanical cues, offer a promising therapeutic approach to help axons overcome this blind journey. We used poly(3,4-ethylenedioxythiophene)-coated carbon MFs functionalized with cell adhesion molecules and growth factors to bridge the spinal cord after a partial unilateral dorsal quadrant lesion (PUDQL) in mice and followed cellular responses by intravital two-photon (2P) imaging through a spinal glass window. Thy1-CFP//LysM-EGFP//CD11c-EYFP triple transgenic reporter animals allowed real time simultaneous monitoring of axons, myeloid cells and microglial cells in the vicinity of the implanted MFs. MF biocompatibility was confirmed by the absence of inflammatory storm after implantation. We found that the sprouting of sensory axons was significantly accelerated by the implantation of functionalized MFs after PUDQL. Their implantation produced better axon alignment compared to random and misrouted axon regeneration that occurred in the absence of MF, with a most striking effect occurring two months after injury. Importantly, we observed differences in the intensity and composition of the innate immune response in comparison to PUDQL-only animals. A significant decrease of immune cell density was found in MF-implanted mice one month after lesion along with a higher ratio of monocyte-derived dendritic cells whose differentiation was accelerated. Therefore, functionalized carbon MFs promote the beneficial immune responses required for neural tissue repair, providing an encouraging strategy for SCI management. |
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spelling | doaj.art-de35fb344e7b4c0780f125a93a05d14c2023-11-21T08:22:11ZengMDPI AGCells2073-44092021-01-011017310.3390/cells10010073Intravital Assessment of Cells Responses to Conducting Polymer-Coated Carbon Microfibres for Bridging Spinal Cord InjuryBilal El Waly0Vincent Escarrat1Jimena Perez-Sanchez2Jaspreet Kaur3Florence Pelletier4Jorge Eduardo Collazos-Castro5Franck Debarbieux6Institut des Neurosciences de la Timone (UMR7289), Aix-Marseille Université and Centre National de la Recherche Scientifique, 13005 Marseille, FranceInstitut des Neurosciences de la Timone (UMR7289), Aix-Marseille Université and Centre National de la Recherche Scientifique, 13005 Marseille, FranceInstitut des Neurosciences de la Timone (UMR7289), Aix-Marseille Université and Centre National de la Recherche Scientifique, 13005 Marseille, FranceInstitut des Neurosciences de la Timone (UMR7289), Aix-Marseille Université and Centre National de la Recherche Scientifique, 13005 Marseille, FranceInstitut des Neurosciences de la Timone (UMR7289), Aix-Marseille Université and Centre National de la Recherche Scientifique, 13005 Marseille, FranceNeural Repair and Biomaterials Laboratory, Hospital Nacional de Parapléjicos (SESCAM), 45071 Toledo, SpainInstitut des Neurosciences de la Timone (UMR7289), Aix-Marseille Université and Centre National de la Recherche Scientifique, 13005 Marseille, FranceThe extension of the lesion following spinal cord injury (SCI) poses a major challenge for regenerating axons, which must grow across several centimetres of damaged tissue in the absence of ordered guidance cues. Biofunctionalized electroconducting microfibres (MFs) that provide biochemical signals, as well as electrical and mechanical cues, offer a promising therapeutic approach to help axons overcome this blind journey. We used poly(3,4-ethylenedioxythiophene)-coated carbon MFs functionalized with cell adhesion molecules and growth factors to bridge the spinal cord after a partial unilateral dorsal quadrant lesion (PUDQL) in mice and followed cellular responses by intravital two-photon (2P) imaging through a spinal glass window. Thy1-CFP//LysM-EGFP//CD11c-EYFP triple transgenic reporter animals allowed real time simultaneous monitoring of axons, myeloid cells and microglial cells in the vicinity of the implanted MFs. MF biocompatibility was confirmed by the absence of inflammatory storm after implantation. We found that the sprouting of sensory axons was significantly accelerated by the implantation of functionalized MFs after PUDQL. Their implantation produced better axon alignment compared to random and misrouted axon regeneration that occurred in the absence of MF, with a most striking effect occurring two months after injury. Importantly, we observed differences in the intensity and composition of the innate immune response in comparison to PUDQL-only animals. A significant decrease of immune cell density was found in MF-implanted mice one month after lesion along with a higher ratio of monocyte-derived dendritic cells whose differentiation was accelerated. Therefore, functionalized carbon MFs promote the beneficial immune responses required for neural tissue repair, providing an encouraging strategy for SCI management.https://www.mdpi.com/2073-4409/10/1/73dorsal hemisectiontransgenic multifluorescent micemicrofibre scaffoldaxonal regenerationtwo photon imagingmicroglia |
spellingShingle | Bilal El Waly Vincent Escarrat Jimena Perez-Sanchez Jaspreet Kaur Florence Pelletier Jorge Eduardo Collazos-Castro Franck Debarbieux Intravital Assessment of Cells Responses to Conducting Polymer-Coated Carbon Microfibres for Bridging Spinal Cord Injury Cells dorsal hemisection transgenic multifluorescent mice microfibre scaffold axonal regeneration two photon imaging microglia |
title | Intravital Assessment of Cells Responses to Conducting Polymer-Coated Carbon Microfibres for Bridging Spinal Cord Injury |
title_full | Intravital Assessment of Cells Responses to Conducting Polymer-Coated Carbon Microfibres for Bridging Spinal Cord Injury |
title_fullStr | Intravital Assessment of Cells Responses to Conducting Polymer-Coated Carbon Microfibres for Bridging Spinal Cord Injury |
title_full_unstemmed | Intravital Assessment of Cells Responses to Conducting Polymer-Coated Carbon Microfibres for Bridging Spinal Cord Injury |
title_short | Intravital Assessment of Cells Responses to Conducting Polymer-Coated Carbon Microfibres for Bridging Spinal Cord Injury |
title_sort | intravital assessment of cells responses to conducting polymer coated carbon microfibres for bridging spinal cord injury |
topic | dorsal hemisection transgenic multifluorescent mice microfibre scaffold axonal regeneration two photon imaging microglia |
url | https://www.mdpi.com/2073-4409/10/1/73 |
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