Rapidly-Gelling, Guanosine 5' Diphosphate-Crosslinked Injectable Chitosan Sponges to Promote Oligodendrocyte Progenitor Cells' Differentiation Post-Spinal Cord Injuries

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In Canada, there are approximately 86,000 Canadians living with spinal cord injuries (SCI). The economic burden caused by SCI is immense, costing Canada an estimated $3.6 billion/Y. The initial trauma causes a contusion injury to the spinal cord resulting in damage to neurons and oligodendrocytes (OLGs). Secondary to trauma, there is additional neuronal and axonal loss, and damage to myelin and glia. The loss of myelin surrounding intact axons (demyelination) can result in functional loss because of the inability of these axons to effectively conduct nerve impulses. At present there are no effective treatments for SCI, and although many researchers are interested in neural regeneration, none are focused on developing biomaterials to target remyelination post-SCI. Therefore, the overall objective of this proposal is to use an injectable scaffold containing neurotrophic factors to promote the differentiation of endogenous OPCs and improve remyelination and neurological function post-SCI. We successfully developed a novel, rapidly-gelling, injectable chitosan sponge using Guanosine 5-diphosphate (GDP). The sponges gel in less than 2 seconds, a highly desirable property to ensure localization at the site of injection. Moreover, the sponges were found to have very desirable physicochemical properties and excellent cytocompatibility. Brain Derived Neurotrophic Factor (BDNF) was successfully entrapped and released from the sponges in a controlled manner for up to 3 weeks. Furthermore, we demonstrated the successful attachment and differentiation of rat OPCs' on the chitosan sponges. Further studies are still required using rat OPCs to investigate myelination on the sponges. Furthermore, fetal and adult human OPCs survival and differentiation on the sponges will be assessed. Finally, chitosan sponges will be injected in a contused mouse spinal cord model to study remyelination and recovery of neurological functions.