A Protein-Polymer Approach to Neural Tissue Regeneration

神经组织再生的蛋白质聚合物方法

• 批准号: 6893395
• 负责人: Kim Janda
• 金额: $ 21.7万
• 依托单位: SCRIPPS RESEARCH INSTITUTE, THE
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-07-01 至 2006-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6893395
• 关键词: bioassay; bioengineering /biomedical engineering; biomaterial compatibility; biomaterial development /preparation; biomaterial evaluation; biomaterial interface interaction; biotechnology; confocal scanning microscopy; enzyme linked immunosorbent assay; gel; green fluorescent proteins; liquid chromatography mass spectrometry; nervous system regeneration; neurotrophic factors; nuclear matrix; peptide chemical synthesis; spinal cord injury; tissue support frame

DESCRIPTION (provided by applicant): There are an estimated 8,000 to 10,000 new cases of spinal cord injury in the United States each year. While most victims survive, virtually all are left with partial to permanent paralysis and limited prospects for improvement. Although work in recent years has vastly improved our understanding of the molecular and cellular biology of the healing process following spinal cord injuries, translation of these findings to practical, clinical use has been limited. We propose to apply the tools of peptide and polymer chemistry to construct a highly well-defined polymeric matrix that will support neural tissue regeneration in the injured spinal cord. This growth matrix will be not only biocompatible, but bioactive - tailored at the molecular level with specific growth cues to provide functional assistance to tissue regeneration. Specifically, the aims of this proposal are (1) chemical synthesis of human neurotrophin-3 (NT-3), a key growth factor involved in axonal regrowth; (2) preparation of an MMP-degradable hydrogel that will allow for covalent attachment of a suitably functionalized NT-3 analogue; (3) construction of the resulting bioconjugate; and (4) optimization of the performance of the NT-3-grafted hydrogel using combinatorial synthesis techniques coupled with in vitro assays. We envisage that the initial studies described herein will serve as the foundation for further studies in our laboratory in the design and chemical synthesis of biomimetic tissue regeneration matrices.

描述（由申请人提供）： 每年，美国估计有8,000至10,000例新的脊髓损伤病例。尽管大多数受害者都能生存，但几乎所有受害者都属于永久性瘫痪和改善前景有限。尽管近年来的工作大大改善了我们对脊髓损伤后愈合过程的分子和细胞生物学的理解，但这些发现将这些发现转化为实际，但临床用途受到限制。我们建议应用肽和聚合物化学的工具来构建一个明确定义的聚合物基质，该基质将支持受伤的脊髓中的神经组织再生。该生长基质不仅具有生物相容性，而且将是在分子水平下量身定制的，并具有特定的生长提示，以为组织再生提供功能辅助。具体而言，该提案的目的是（1）人类神经营养蛋白3（NT-3）的化学合成，这是轴突再生涉及的关键生长因子； （2）制备MMP降解水凝胶，该水凝胶将允许合适的NT-3类似物的共价附着； （3）构建所得的生物缀合物； （4）使用联合合成技术与体外测定相结合的组合合成技术来优化NT-3枝的水凝胶的性能。我们设想，本文所述的最初研究将成为我们实验室在仿生组织再生矩阵的设计和化学合成方面进一步研究的基础。