CAREER: Study of Astrocyte Migration and Reactivity Using Novel Biomaterial Platforms

该职业奖由伦斯勒理工学院材料研究部生物材料项目颁发，旨在开发新型生物材料和细胞培养技术，以调节星形胶质细胞的反应性。脊髓损伤后瘢痕组织中形成的星形胶质细胞形成屏障，阻碍轴突的再生和脊髓损伤后的恢复。本研究旨在开发可减弱脊髓损伤后星形胶质细胞反应的生物材料，并构建支持轴突通过神经胶质-瘢痕界面迁移的新型生物材料。为了减弱星形胶质细胞的反应，不同的肽和蛋白质将在排列的聚合物纤维衬底中掺杂。将星形胶质细胞植入纳米纤维基质，并评估以下参数：1)动态和静态星形胶质细胞迁移；2)星形胶质细胞活化/反应性分子生物学技术；3)利用原子力显微镜观察星形胶质细胞的刚度。将开发含有氧化铁纳米颗粒的聚合物球，并将其与化学引诱剂（如环磷酸腺苷和脑源性神经营养因子）结合，以创建磁性可移动的化学引诱剂梯度。这些可移动的梯度有望通过星形胶质细胞或抑制性蛋白多糖聚集蛋白促进轴突生长锥的定向延伸。该提案支持本科生和研究生在开发新型生物材料支架，星形胶质细胞和神经元的分离和培养方面的教育。此外，学生将接受使用分子生物学和先进显微镜技术评估细胞行为的培训。脊髓损伤的人会失去受伤部位以下的身体功能，导致终身瘫痪。目前，没有FDA批准的生物、药理学和/或生物材料治疗方法可以恢复失去的功能。这项提议的目标是开发新的生物材料来减弱或消除星形胶质细胞的反应性，星形胶质细胞是脊髓瘢痕组织中发现的一种胶质细胞，已知会产生抑制神经再生的因子。此外，磁诱导聚合物球将开发引导轴突通过抑制域。这些生物材料可以减少星形胶质细胞的抑制性质，有助于促进神经轴突的定向迁移和再生。本提案中提出的实验将为开发脊髓损伤的新策略和治疗方法提供框架。此外，该提案还支持本科生和研究生在脊髓损伤研究和生物材料制造领域的教育。此外，该提案还支持对小学、初中和高中学生以及公众进行脊髓损伤和生物材料领域教育的倡议。

This Career award by the Biomaterials program in the Division of Materials Research to Rensselaer Polytechnic Institute is to develop novel biomaterials and cell culture techniques that modulate the reactivity of astrocytes. Astrocytes formed in the scar tissues after spinal cord injury create a barrier, and this barrier prevents the regeneration of axons and recovery from spinal cord injury. This proposal aims to develop biomaterials that attenuate astrocyte response following spinal cord injury and construct novel biomaterial approaches to support axonal migration through glial-scar interfaces. To attenuate astrocyte response, different peptides and proteins will be doped within aligned polymer fiber substrates. Astrocytes will be seeded onto the nanofiber substrates and the following parameters will be assessed: 1) dynamic and static astrocyte migration; 2) astrocyte activation/reactivity using molecular biology techniques; and 3) astrocyte stiffness using atomic force microscopy. Polymer spheres containing iron oxide nanoparticles with the chemo-attractants such as cyclic adenosine monophophate and brain derived neurotrophic factor will be developed to create magnetically moveable chemo-attractant gradients. These moveable gradients are expected to foster the directed extension of axonal growth cones through astrocytes or the inhibitory proteoglycan aggrecan. The proposal supports the education of undergraduate and graduate students in developing novel biomaterial scaffolds, isolation and culture of astrocytes and neurons. In addition, students will be trained in the assessment of cellular behavior using molecular biology and advanced microscopy techniques. Individuals with spinal cord injury lose body functions below the site of injury leading to life-long paralysis. At present, no FDA approved biological, pharmacological, and/or biomaterial treatments exist to restore the lost functions. The goal of this proposal is to develop novel biomaterials to attenuate or eliminate the reactivity of astrocytes, a glial cell found in the scar tissues of the spinal cord that are known to produce factors inhibiting the nerve regeneration. Additionally, magnetically inducible polymer spheres will be developed to guide axons through inhibitory domains. It is believed that these biomaterials can reduce the inhibitory nature of astrocytes and help promote directed migration and regeneration of nerve axons. The experiments proposed within this proposal will provide the framework for developing novel strategies and treatments for spinal cord injury. In addition, the proposal supports the education of undergraduates and graduate students in the areas of spinal cord injury research and biomaterial fabrication. Further, the proposal supports initiatives to educate students from elementary, junior high school and high school, and the general public about spinal cord injury and the field of biomaterials.