Bioactive Scaffolds for Regeneration in Spinal Cord Injury

描述（由申请人提供）：中枢神经系统（CNS）是高度复杂的特化细胞集合，其成功的功能依赖于有效的细胞通讯，以在所有身体组织和系统中传输信号信息。对这些细胞的损伤，无论是通过有毒分子或过程，机械应力，还是与年龄相关的/遗传疾病，都会导致这种通信的中断和随后的细胞死亡。因此，在这些损伤后恢复CNS功能的再生医学程序在医学界至关重要。然而，成年人体内发育完全的中枢神经系统在失去时再生组织和形成这些必要的新细胞连接的能力有限。该领域的巨大需求包括治疗脊髓损伤（SCI）以预防或逆转瘫痪的疗法，中风和神经退行性疾病的新疗法，以及恢复视神经和听觉神经功能的策略。新疗法可以大大提高面临这些问题的个人的生活质量，并显着降低医疗保健成本。例如，仅在美国，SCI每年影响12，000人，目前约有259，000美国人生活在SCI的破坏性影响中。中枢神经系统再生的新治疗方法将对医疗保健和患者健康产生重大影响。在这项更新申请中，来自医学，化学和材料科学的三名研究人员提出研究开发可用于预防脊髓损伤后瘫痪的疗法，以及一种可以通过手术植入来逆转瘫痪的不同疗法。该方法涉及使用被称为肽两亲物的特别设计的分子，该分子在脊髓中自组装成纳米纤维。这些纳米纤维携带生物信号，促进创伤组织的再生，并在几周内生物降解成无害的营养物质。具体的策略涉及使用几种基于肽的信号，这些信号模仿天然蛋白质的作用，并且还递送将导致再生生长因子在脐带中产生的基因。对于急性损伤，治疗采用可注射液体的形式，对于慢性损伤，治疗包括在瘫痪患者中移除胶质瘢痕后放置的预制凝胶植入物。两种疗法都将在完善的脊髓损伤小鼠模型中进行测试。 公共卫生相关性：在美国，每年大约有12，000例脊髓损伤新发病例。脊髓损伤最常由事故引起，它主要影响年轻人，据估计，目前有259，000美国人生活在其破坏性影响中。这项研究计划旨在开发可以预防或逆转脊髓损伤后瘫痪的疗法。

DESCRIPTION (provided by applicant): The central nervous system (CNS) is a highly complex collection of specialized cells whose successful function relies on effective cellular communication to transport signal information across all the body's tissues and systems. Injury to these cells, whether through toxic molecules or processes, mechanical stresses, or age-related/genetic illnesses, leads to the breakdown of this communication and subsequent cell death. Regenerative medicine procedures to regain the functionality of the CNS after these insults is therefore of critical importance in the medical community. However, the fully developed CNS in the adult human body has limited capacity to regenerate tissues and to form these essential new cellular connections when lost. Among the great needs in this field are therapies to treat spinal cord injury (SCI) in order to prevent or reverse paralysis, novel treatments for stroke and neurodegenerative diseases, as well as strategies to recover the function of optic and auditory nerves. New therapies could profoundly enhance quality of life for individuals facing these problems and significantly reduce health care costs as well. For example, in the United States alone, SCI affects 12,000 individuals every year, and approximately 259,000 Americans currently live with the devastating effects of SCI. Novel therapeutic approaches to CNS regeneration will have significant impact on health care and patient well-being. In this renewal application three investigators, from the medical, chemical, and materials sciences, propose research to develop therapies for that could be used to prevent paralysis after spinal cord injury and also a different therapy that could be surgically implanted to reverse paralysis. The approach involves the use of especially designed molecules known as peptide amphiphiles that self-assemble in the spinal cord into nanofibers. These nanofibers carry biological signals that promote regeneration in the traumatized tissue, and biodegrade within weeks into harmless nutrients. The specific strategy involves the use of several peptide-based signals that emulate the effect of natural proteins, and also the delivery of genes that will lead to the production in the cord of regenerative growth factors. For acute injury the therapy takes the form of an injectable liquid, and for the chronic injury it consists of a pre-fabricated gel implant to be placed after removal of the glial scar in paralyzed patients. Both therapies will be tested in well established mouse models for spinal cord injury. PUBLIC HEALTH RELEVANCE: In the United States approximately 12,000 new cases of spinal cord injury occur each year. Spinal cord injury is most often caused by accidents, it primarily affects young adults, and it is estimated that 259,000 Americans currently live with its devastating effects. This research proposal aims to develop therapies that could prevent or reverse paralysis after spinal cord injury.