Regeneration after traumatic spinal cord injury generally fails due to a cascade of cellular and ... more Regeneration after traumatic spinal cord injury generally fails due to a cascade of cellular and molecular events, including blood-spinal cord barrier breakdown,persistent and uncontrolled inflammation, and glial scarring and cavity formation combined with the presence of axon growth-inhibitory molecules. While efficient therapies are still lacking, recent progress in the design of implantable biomaterials may well open up new possibilites for their development. Chitosan hydrogels (hCh) seem particularly promising as their biological properties can be fine-tuned, notably by their degree of acetylation (DA). In the context of a rat dorsal spinal cord hemisection, I have tested different formulations of fragmented hCh for their ability to integrate into lesioned host tissue without creating additional inflammation, or excessive astrocytic reaction. Thus, I found that implantation of hCh particles of 4% DA allows for tissue reconstruction by attracting different cell types and recreating a functional vasculature. Importantly, it modulates the inflammatory response, favoring polarization of invading macrophages towards the M2 phenotype. In lesioned-implanted animals, the glial scar is less fibrous, astrocyte processes are mainly oriented towards the lesion and accompany a robust regrowth of fibers, whose origin was identified by axon tracing and immunohistochemistry. Many of these fibers are myelinated or ensheathed by Schwann cells, maintained at long term in the implant. Finally, this structural remodeling is associated with significant, long-lasting recovery of locomotor function, as I have shown by open-field and gait analysis.
La régénération après une lésion de la moelle épinière (ME) est abortive. Elle est du à une casca... more La régénération après une lésion de la moelle épinière (ME) est abortive. Elle est du à une cascade d'événements cellulaires et moléculaires, dont la rupture de la barrière hémato-encéphalique, une inflammation persistante, une cicatrice gliale et la formation d'une cavité, combinée à la présence de molécules inhibitrices pour la repousse. Actuellement, aucune thérapie n'est efficace, mais le design de biomatériaux implantables pourrait permettre leur développement. L'hydrogel de chitosane (hCh) apparait prometteur, notamment grâce à la modulation de ses propriétés biologiques, notamment en modifiant son degré de déacétylation (DA). J'ai donc testé, dans une hémisection dorsale de la ME de rat, différentes formulations d'hCh fragmenté et examiné leur capacité à s'intégrer dans le tissu hôte lésé, sans produire une inflammation ou une réaction astrocytaire excessive. Mon travail montre que l'implantation de fragments d'hCh avec un DA de 4% est favo...
Regeneration after traumatic spinal cord injury generally fails due to a cascade of cellular and ... more Regeneration after traumatic spinal cord injury generally fails due to a cascade of cellular and molecular events, including blood-spinal cord barrier breakdown,persistent and uncontrolled inflammation, and glial scarring and cavity formation combined with the presence of axon growth-inhibitory molecules. While efficient therapies are still lacking, recent progress in the design of implantable biomaterials may well open up new possibilites for their development. Chitosan hydrogels (hCh) seem particularly promising as their biological properties can be fine-tuned, notably by their degree of acetylation (DA). In the context of a rat dorsal spinal cord hemisection, I have tested different formulations of fragmented hCh for their ability to integrate into lesioned host tissue without creating additional inflammation, or excessive astrocytic reaction. Thus, I found that implantation of hCh particles of 4% DA allows for tissue reconstruction by attracting different cell types and recreati...
Recovery from traumatic spinal cord injury (SCI) usually fails due to a cascade of cellular and m... more Recovery from traumatic spinal cord injury (SCI) usually fails due to a cascade of cellular and molecular events that compromise neural tissue reconstitution by giving rise to glial scarring and cavity formation. We designed a scaffold material for SCI treatment containing only chitosan and water as fragmented physical hydrogel suspension (Chitosan-FPHS), with defined degree of acetylation (DA), polymer concentration, and mean fragment size. Implantation of Chitosan-FPHS alone into rat spinal cord immediately after a bilateral dorsal hemisection promoted reconstitution of spinal tissue and vasculature, and diminished fibrous glial scarring: with astrocyte processes primarily oriented towards the lesion, the border between lesion site and intact tissue became permissive for regrowth of numerous axons into, and for some even beyond the lesion site. Growing axons were myelinated or ensheathed by endogenous Schwann cells that migrated into the lesion site and whose survival was prolonge...
Regeneration after traumatic spinal cord injury generally fails due to a cascade of cellular and ... more Regeneration after traumatic spinal cord injury generally fails due to a cascade of cellular and molecular events, including blood-spinal cord barrier breakdown,persistent and uncontrolled inflammation, and glial scarring and cavity formation combined with the presence of axon growth-inhibitory molecules. While efficient therapies are still lacking, recent progress in the design of implantable biomaterials may well open up new possibilites for their development. Chitosan hydrogels (hCh) seem particularly promising as their biological properties can be fine-tuned, notably by their degree of acetylation (DA). In the context of a rat dorsal spinal cord hemisection, I have tested different formulations of fragmented hCh for their ability to integrate into lesioned host tissue without creating additional inflammation, or excessive astrocytic reaction. Thus, I found that implantation of hCh particles of 4% DA allows for tissue reconstruction by attracting different cell types and recreating a functional vasculature. Importantly, it modulates the inflammatory response, favoring polarization of invading macrophages towards the M2 phenotype. In lesioned-implanted animals, the glial scar is less fibrous, astrocyte processes are mainly oriented towards the lesion and accompany a robust regrowth of fibers, whose origin was identified by axon tracing and immunohistochemistry. Many of these fibers are myelinated or ensheathed by Schwann cells, maintained at long term in the implant. Finally, this structural remodeling is associated with significant, long-lasting recovery of locomotor function, as I have shown by open-field and gait analysis.
La régénération après une lésion de la moelle épinière (ME) est abortive. Elle est du à une casca... more La régénération après une lésion de la moelle épinière (ME) est abortive. Elle est du à une cascade d'événements cellulaires et moléculaires, dont la rupture de la barrière hémato-encéphalique, une inflammation persistante, une cicatrice gliale et la formation d'une cavité, combinée à la présence de molécules inhibitrices pour la repousse. Actuellement, aucune thérapie n'est efficace, mais le design de biomatériaux implantables pourrait permettre leur développement. L'hydrogel de chitosane (hCh) apparait prometteur, notamment grâce à la modulation de ses propriétés biologiques, notamment en modifiant son degré de déacétylation (DA). J'ai donc testé, dans une hémisection dorsale de la ME de rat, différentes formulations d'hCh fragmenté et examiné leur capacité à s'intégrer dans le tissu hôte lésé, sans produire une inflammation ou une réaction astrocytaire excessive. Mon travail montre que l'implantation de fragments d'hCh avec un DA de 4% est favo...
Regeneration after traumatic spinal cord injury generally fails due to a cascade of cellular and ... more Regeneration after traumatic spinal cord injury generally fails due to a cascade of cellular and molecular events, including blood-spinal cord barrier breakdown,persistent and uncontrolled inflammation, and glial scarring and cavity formation combined with the presence of axon growth-inhibitory molecules. While efficient therapies are still lacking, recent progress in the design of implantable biomaterials may well open up new possibilites for their development. Chitosan hydrogels (hCh) seem particularly promising as their biological properties can be fine-tuned, notably by their degree of acetylation (DA). In the context of a rat dorsal spinal cord hemisection, I have tested different formulations of fragmented hCh for their ability to integrate into lesioned host tissue without creating additional inflammation, or excessive astrocytic reaction. Thus, I found that implantation of hCh particles of 4% DA allows for tissue reconstruction by attracting different cell types and recreati...
Recovery from traumatic spinal cord injury (SCI) usually fails due to a cascade of cellular and m... more Recovery from traumatic spinal cord injury (SCI) usually fails due to a cascade of cellular and molecular events that compromise neural tissue reconstitution by giving rise to glial scarring and cavity formation. We designed a scaffold material for SCI treatment containing only chitosan and water as fragmented physical hydrogel suspension (Chitosan-FPHS), with defined degree of acetylation (DA), polymer concentration, and mean fragment size. Implantation of Chitosan-FPHS alone into rat spinal cord immediately after a bilateral dorsal hemisection promoted reconstitution of spinal tissue and vasculature, and diminished fibrous glial scarring: with astrocyte processes primarily oriented towards the lesion, the border between lesion site and intact tissue became permissive for regrowth of numerous axons into, and for some even beyond the lesion site. Growing axons were myelinated or ensheathed by endogenous Schwann cells that migrated into the lesion site and whose survival was prolonge...
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Papers by Jamila CHEDLY