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

这项由伦斯勒理工学院材料研究部生物材料项目授予伦斯勒理工学院的职业奖项是开发调节星形胶质细胞反应性的新型生物材料和细胞培养技术。脊髓损伤后在瘢痕组织中形成的星形胶质细胞形成屏障，这种屏障阻碍轴突的再生和脊髓损伤的恢复。这项建议旨在开发生物材料，以减弱脊髓损伤后星形胶质细胞的反应，并构建新的生物材料途径，以支持轴突通过神经胶质-瘢痕界面的迁移。为了减弱星形胶质细胞的反应，不同的多肽和蛋白质将被掺入排列的聚合物纤维基质中。星形胶质细胞将被种植到纳米纤维基质上，并将评估以下参数：1)星形胶质细胞的动态和静态迁移；2)星形胶质细胞的激活/反应；3)原子力显微镜下的星形胶质细胞硬度。含有氧化铁纳米颗粒和化学引诱剂的聚合物球体将被开发出来，以产生磁性可移动的化学引诱剂梯度。这些可移动的梯度有望促进轴突生长锥体通过星形胶质细胞或抑制蛋白多糖凝集蛋白的定向延伸。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，学生还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。脊髓损伤患者在损伤部位以下丧失身体功能，导致终生瘫痪。目前，还没有FDA批准的生物、药物和/或生物材料治疗方法来恢复丧失的功能。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，星形胶质细胞是一种在脊髓疤痕组织中发现的胶质细胞，已知会产生抑制神经再生的因素。此外，还将开发磁性可诱导聚合物球来引导轴突通过抑制域。据认为，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。这项提议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，该提案还支持在脊髓损伤研究和生物材料制造领域对本科生和研究生进行教育。此外，该提案还支持对小学、初中和高中的学生以及普通公众进行脊髓损伤和生物材料领域的教育。

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.