BIORESORBABLE MICROFILAMENTS FOR NERVOUS SYSTEM REPAIR

已知周围神经移植物支持轴突再生穿过中枢神经系统中的损伤或周围神经系统中的损伤神经间隙。通过这些神经节段的增强的轴突生长最有可能是由神经营养因子、粘附分子和促进生长的细胞外基质分子如层粘连蛋白的产生增加引起的。这些神经节段还包含用于组织和指导轴突生长的通道。这项建议将测试的假设，即模仿周围神经移植物的特征的人工基质将影响胶质细胞的附着，迁移，并增强轴突再生。为了验证这一假设，我们构建了生物可吸收的聚合物，可以修改，以促进轴突生长和释放神经营养因子的微丝。当这些微丝成束时，它们提供了定向细胞迁移和轴突生长的通道。为了更全面地了解细胞-材料相互作用，将从两种具有选择性物理和生物化学性质的聚合物中制造微丝，并在植入坐骨神经或脊髓后进行检查。为了检查细胞对物理性质变化的反应，将改变孔隙率、蛋白质释放速率、横截面形状和细丝直径。初级聚合物还具有不同的生物化学性质，可以通过掺入细胞外基质分子（基质胶或层粘连蛋白）或神经营养因子来进一步修饰。这些生化修饰应该通过提供必要的趋化性和化学亲和性信号，极大地影响微丝与胶质细胞和再生轴突的相互作用。本研究最重要的方面是巩固和利用物理和生物化学性质来探索、影响和组织细胞-材料相互作用，以增强整合、伤口愈合和再生。 将使用免疫组织学、半薄塑料切片和电子显微镜检查对微丝植入物的细胞反应。这些实验将更好地理解细胞如何与生物可吸收材料相互作用，以及如何通过改变材料的物理和生化特性来操纵这些相互作用。这项研究的最终目标是更好地了解影响损伤修复的机制，并利用这些见解来改善可促进伤口愈合和神经系统再生的生物材料的开发和制造。

Peripheral nerve grafts are known to support axonal regeneration across a lesion in the central nervous system or a lesioned nerve gap in the peripheral nervous system. Enhanced axon growth through these nerve segments is most likely caused by increased production of neurotrophins, adhesion molecules, and growth promoting extracellular matrix molecules such as laminin. These nerve segments also contain channels that act to Organize and direct axon growth. This proposal will test the hypothesis that an artificial matrix mimicking the features of peripheral nerve grafts will influence glial attachment, migration, and enhance axonal regeneration. To test this hypothesis, we constructed microfilaments from bioresorbable polymers that can be modified to promote axon growth and release neurotrophins. When bundled, these microfilaments provide channels that orient cell migration and axonal growth. To develop a more complete understanding of cellular-material interaction, microfilaments will be fabricated from two polymers with selective physical and biochemical properties and examined after implantation into either the sciatic nerve or spinal cord. To examine cell responses to changes in physical properties, porosity, protein-release rates, cross-sectional shape, and filament diameters will be altered. The primary polymers also have different biochemical properties that can be further modified by incorporating extracellular matrix molecules (matrigel Or laminin) or neurotrophins. These biochemical modifications should greatly influence microfilament interactions with glia and regenerating axons by providing necessary chemotactic and chemoaffinity signals. The most important aspect of this study is the consolidation and utilization of both the physical and biochemical properties to explore, influence, and organize the cellular- material interaction to enhance integration, wound healing, and regeneration. Cellular responses to microfilament implants will be examined using immunohistology, semi-thin plastic sections, and electron microscopy. These experiments will elicit a better understanding of how cells interact with bioresorbable materials and how these interactions can be manipulated by altering the physical and biochemical properties of the material. The ultimate goal of this research is to achieve a better understanding of the mechanisms that influence injury repair and to use these insights to improve the development and fabrication of biomaterials that can promote wound healing and regeneration of the nervous system.