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

在加拿大，大约有86，000名加拿大人患有脊髓损伤（SCI）。造成的经济负担 SCI是巨大的，加拿大估计每年花费36亿美元。最初的创伤导致脊髓挫伤 导致神经元和少突胶质细胞（OLG）损伤。继发于创伤，有额外的神经元和轴突 髓鞘和神经胶质的损失和损伤。完整轴突周围髓鞘的丢失（脱髓鞘）可导致功能丧失 因为这些轴突不能有效地传导神经冲动。目前尚无有效的治疗方法， 尽管许多研究人员对神经再生感兴趣，但没有人专注于开发生物材料， 目标是脊髓损伤后髓鞘再生。因此，该提案的总体目标是使用可注射支架，其包含： 神经营养因子促进内源性OPCs的分化，改善髓鞘再生和神经功能 SCI后。我们成功地开发了一种新型的，快速凝胶化，可注射壳聚糖海绵使用鸟苷5-二磷酸 （国内生产总值）。海绵在不到2秒内凝胶化，这是确保注射部位定位的非常理想的特性。 此外，海绵被发现具有非常理想的物理化学性质和优异的细胞相容性。大脑 衍生的神经营养因子（BDNF）成功地被捕获，并以受控的方式从海绵中释放， 最多3周。此外，我们还证明了大鼠OPCs在壳聚糖上的成功附着和分化 海绵仍需要进一步的研究，使用大鼠OPCs来研究海绵上的髓鞘形成。此外，胎儿和 评估成年人OPCs在海绵上的存活和分化。最后，将壳聚糖海绵注入 一种用于研究髓鞘再生和神经功能恢复的挫伤小鼠脊髓模型。

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.