BIORESORBABLE MICROFILAMENTS FOR NERVOUS SYSTEM REPAIR

已知的是，周围神经移植物可以通过中枢神经系统的损伤或周围神经系统受损的神经间隙支持轴突再生。通过这些神经节段促进轴突生长很可能是由于神经营养因子、黏附分子和促进生长的细胞外基质分子(如层粘连蛋白)的产生增加所致。这些神经节还含有组织和引导轴突生长的通道。这项提议将检验这样一种假设，即模仿周围神经移植物特征的人工基质将影响神经胶质附着、迁移和促进轴突再生。为了验证这一假设，我们从生物可吸收聚合物中构建了微丝，这种聚合物可以被修饰以促进轴突生长和释放神经营养因子。当这些微丝捆绑在一起时，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与材料的相互作用，将由两种具有选择性物理和生化特性的聚合物制成微丝，并在植入坐骨神经或脊髓后进行检查。为了检测细胞对物理性质变化的反应，孔隙率、蛋白质释放率、横截面形状和细丝直径将被改变。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(片层或层粘连蛋白)或神经营养因子来进一步修饰。这些生化修饰将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。这项研究最重要的方面是巩固和利用物理和生化特性来探索、影响和组织细胞与材料的相互作用，以促进整合、伤口愈合和再生。细胞对微丝植入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。这些实验将使人们更好地理解细胞如何与可生物吸收材料相互作用，以及如何通过改变材料的物理和生化性质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进可以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.