Rational and Combinatorial Design of Biomaterials for Neural Engineering

神经工程生物材料的合理组合设计

• 批准号: 1067208
• 负责人: Deanna Thompson
• 金额: $ 33万
• 依托单位: Rensselaer Polytechnic Institute
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-07-15 至 2015-12-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1067208&HistoricalAwards=false
• 关键词: Rational; Combinatorial; Design; Biomaterials; Neural

1067208ThompsonSeveral factors such as formation of scar tissue, inadequate removal of inhibitory myelin, cell death and lack of a permissive substrate or growth factors limit the ability of neurons to regenerate after an injury. The guiding rationale is that a tissue-specific biomaterial designed for both resident neural (sensory and motor neurons) and resident non-neural cells (Schwann cells and endothelial cells) of the peripheral nervous system combined with the appropriate soluble factors can serve as the foundation for a superior nerve guidance channel to address these challenges. Rational and combinatorial design strategies for the discovery of synergistic extracellular matrix proteins and soluble factors combinations generating a tissue-specific biomaterial for regenerating axons and support cells will be applied in a physiologically-relevant 3-dimensional environment. The objective is to systematically screen a large subset of matrix proteins, base scaffolds and soluble factors combinations to rationally design composite biomaterials for the peripheral nervous system. The long-term goal is to engineer a biomaterial for treatment of large-gap peripheral nerve injuries. Novel high throughput screening platforms, such as those proposed in this study, will accelerate the discovery of therapeutically relevant biomaterials for large-gap injuries of the peripheral nerve. This flexible platform can be further extended to screen for materials optimal for spinal cord injury, traumatic brain injury, and cell-based therapies for neurodegenerative diseases.Intellectual Merit: If successful, the proposed research will (1) develop a new framework to examine a prohibitively large experimental space for possible combinations of proteins, scaffolds and soluble factors that by conventional methods due to the time, effort and cost (2) identify cell-specific, novel biomaterial that will serve as a basis of a guidance channel to both promote neuronal growth and/or the migration/re-population of non-neuronal cells relevant to peripheral nerve injury, (3) translation of biomaterials relevant to large-gap peripheral nerve injury to injuries in the brain or spinal cord and (4) apply this high-throughput screening platform rationally generate biomaterial candidates for other target tissues of interest. Broader Impact: If successful, (1) the proposed research will develop a biomaterial to support nerve repair. (2) The research will include the participation of both high school students and undergraduate researchers. (3) Research findings will be broadly disseminated at national/regional meetings, manuscripts in peer-reviewed journals, and invited lectures. (4) Both Principal Investigators and graduate students funded by this project will volunteer by presenting short workshops broadly based on neural engineering to encourage K-12 interest in the Science, Technology, Engineering and Medicine (STEM fields).

1067208 Thompson有几个因素限制了神经元在损伤后再生的能力，如疤痕组织的形成、抑制髓鞘的去除不充分、细胞死亡以及缺乏允许的底物或生长因子。其指导原理是，为周围神经系统的驻留神经(感觉和运动神经元)和驻留的非神经细胞(雪旺细胞和内皮细胞)设计的组织特异性生物材料，结合适当的可溶性因子，可以作为更好的神经引导通道的基础来应对这些挑战。发现协同的细胞外基质蛋白和可溶性因子组合的合理和组合设计策略将应用于与生理相关的三维环境中，以生成用于再生轴突和支持细胞的组织特异性生物材料。本研究的目的是系统地筛选大量的基质蛋白、基质支架和可溶性因子组合，以合理设计用于周围神经系统的复合生物材料。长期目标是设计一种用于治疗大间隙周围神经损伤的生物材料。新的高通量筛选平台，如本研究中提出的平台，将加速发现治疗大间隙周围神经损伤的相关生物材料。这个灵活的平台可以进一步扩展到筛选最适合脊髓损伤、创伤性脑损伤和神经退行性疾病的基于细胞的疗法的材料。智能优点：如果成功，建议的研究将(1)开发一个新的框架，以检查蛋白质、支架和可溶性因子的可能组合的巨大实验空间，由于时间、精力和成本的原因，(2)识别细胞特定的新生物材料，这些材料将作为引导通道的基础，以促进神经元生长和/或与周围神经损伤相关的非神经元细胞的迁移/再繁殖，(3)将与大间隙周围神经损伤相关的生物材料转化为脑或脊髓损伤；(4)应用该高通量筛选平台，合理地为其他感兴趣的靶组织生成生物材料候选。更广泛的影响：如果成功，(1)拟议的研究将开发一种支持神经修复的生物材料。(2)研究将包括高中生和本科生的参与。(3)研究成果将在国家/地区会议、同行评议期刊上的手稿和特邀讲座上广泛传播。(4)该项目资助的首席研究人员和研究生将自愿举办广泛以神经工程为基础的短期研讨会，以鼓励K-12学生对科学、技术、工程和医学(STEM领域)的兴趣。