Regenerative biomaterial matrices for traumatic spinal cord repair

International audienceThe ongoing search for novel, efficient therapeutic strategies for treatment of spinal cord injury (SCI) should greatly profit from the recent progress in the production of innovative biomaterials that when implanted into the lesion site, will function both as extracellular matrix substitute, and as bioactive support structure.Accordingly and as first step, we developed a therapeutic strategy based on the use of chitosan polymer, that exhibits ideal characteristics for tissue engineering. Biological evaluation of diverse formulations (varying in physical and chemicals features) allowed determining the formulations best suited to integrate into spinal cord tissue. Our experimental paradigm is a thoracic dorsal hemisection in adult female rat, with or without implantation of polymer directly after the lesion. Indeed, implantation of the selected chitosan hydrogel formulation induces (i) strong reduction of the astrocytic reaction, (ii) functional vascularization within the implant, (iii) modulated inflammatory response (iv), and most remarkably, growth of a very high number of axons through the implant, evidence for the material per se being extremely favorable for axon regrowth. Finally, these structural remodeling is associated with an improvement of the partial locomotor recovery. Because it effectively induces neural tissue repair, the chitosan biomaterial may be a promising new approach to treat SCI

Chitosan physical microhydrogels as scaffolds for spinal cord injury restoration

International audienceRecovery from traumatic spinal cord injury (SCI) usually fails due to a cascade of cellular andmolecular events that compromise neural tissue reconstitution by giving rise to glial scarring and cavityformation. We designed a scaffold material for SCI treatment containing only chitosan and water asfragmented 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 cordimmediately 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, theborder between lesion site and intact tissue became permissive for regrowth of numerous axons into, andfor some even beyond the lesion site. Growing axons were myelinated or ensheathed by endogenousSchwann cells that migrated into the lesion site and whose survival was prolonged. Interestingly,Chitosan-FPHS also modulated the inflammatory response, and we suggest that this might contribute totissue repair. Finally, this structural remodelling was associated with significant, long-lasting gain inlocomotor function recovery. Because it effectively induces neural tissue repair, Chitosan-FPHSbiomaterial may be a promising new approach to treat SCI, and a suitable substrate to combine with otherstrategies

Physical chitosan microhydrogels as scaffolds for spinal cord injury restoration and axon regeneration

International audienceRecovery 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 prolonged. Interestingly, Chitosan-FPHS also modulated the inflammatory response, and we suggest that this might contribute to tissue repair. Finally, this structural remodeling was associated with significant, long-lasting gain in locomotor function recovery. Because it effectively induces neural tissue repair, Chitosan-FPHS biomaterial may be a promising new approach to treat SCI, and a suitable substrate to combine with other strategies