BIORESORBABLE MICROFILAMENTS FOR NERVOUS SYSTEM REPAIR

已知周围神经移植物可以支持中枢神经系统病变或周围神经系统受损神经间隙的轴突再生。通过这些神经节段的轴突生长增强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。这些神经节段也含有组织和指导轴突生长的通道。这一提议将验证一个假设，即模拟周围神经移植物特征的人工基质将影响神经胶质的附着、迁移和增强轴突再生。为了验证这一假设，我们用生物可吸收聚合物构建了微丝，这种微丝可以被修饰以促进轴突生长并释放神经营养素。当这些微丝捆绑在一起时，它们提供了引导细胞迁移和轴突生长的通道。为了更全面地了解细胞与物质的相互作用，将用两种具有选择性物理和生化特性的聚合物制备微丝，并在植入坐骨神经或脊髓后进行检测。为了检查细胞对物理性质、孔隙度、蛋白质释放率、截面形状和丝直径变化的反应。初级聚合物还具有不同的生化特性，可以通过加入细胞外基质分子（基质或层粘连蛋白）或神经营养素进一步修饰。这些生化修饰应该通过提供必要的趋化和趋化亲和信号，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化特性来探索、影响和组织细胞-物质相互作用，以增强整合、伤口愈合和再生。细胞对微丝植入物的反应将使用免疫组织学、半薄塑料切片和电子显微镜进行检查。这些实验将引出对细胞如何与生物可吸收材料相互作用的更好理解，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理解影响损伤修复的机制，并利用这些见解来改进生物材料的开发和制造，从而促进伤口愈合和神经系统的再生。

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.