Porous Silicon Nanoparticle/Polycaprolactone Composite Nanofibers for Nervous System Repair

用于神经系统修复的多孔硅纳米颗粒/聚己内酯复合纳米纤维

• 批准号: 1603177
• 负责人: Michael Sailor
• 金额: $ 29.87万
• 依托单位: University of California-San Diego
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-06-01 至 2020-05-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1603177&HistoricalAwards=false
• 关键词: Porous; Silicon; Nanoparticle; Polycaprolactone; Composite

PI: Sailor, Michael J.Proposal #: 1603177Nanofiber scaffolds have been used extensively in nerve regeneration strategies; however, current nanofiber technologies lack the ability to fully repair the injured nervous system, often due to difficulty in incorporating sensitive therapeutics into nanofibers caused by the volatile solvents that are used in their fabrication. The proposing group was the first to demonstrate the degradation of porous silicon nanoparticles to non-toxic silicic acid byproducts in-vivo and the first to demonstrate the ability of nanoparticles to be visualized in vivo using gated luminescence imaging. The goal of the proposed research is to build on these results by combining the advantages of porous silicon nanoparticles with polycaprolactone nanofibers, thus developing drug releasing composite nanofibers that can assist in increasing neurite outgrowth and improving nervous system repair. The nanoparticles provide protection of the therapeutics, enhance imaging potential and can be used to alter the degradation process. The nanofibers, whose alignment can be carefully controlled, provide a regenerative substrate that serves to enhance/direct the growth of extending neurites. In summary, if successful, the biodegradable nanofiber scaffolds, which can be easily tuned to alter scaffold degradation rate, photoluminescent intensity, therapeutic delivery, and substrate alignment, will provide an innovative and straightforward model for developing the next-generation of nanofiber scaffolds. Students involved in the research will be provided with a highly interdisciplinary education in materials chemistry, nanoscience, biomedical engineering, and biology. A capstone activity will be a 6-week summer school for silicon nanotechnology, involving high school, undergraduate, and graduate student mentors and mentees. Nanofiber scaffolds have been used extensively in nerve regeneration strategies; however, current nanofiber technologies lack the ability to fully repair the injured nervous system, often due to difficulty in incorporating sensitive therapeutics (such as proteins, siRNA, etc) into nanofibers caused by the volatile solvents that are used in their fabrication. The goal of this three year project is to develop composite nanofibers, in which bioactive therapeutics can be incorporated, with the aim of creating customizable tissue engineering scaffolds for nervous system repair. The proposing group was the first to demonstrate the degradation of porous silicon nanoparticles to non-toxic silicic acid byproducts in-vivo, and the first to demonstrate the ability of nanoparticles to be visualized in vivo using gated luminescence imaging. The aim of this proposal will be accomplished by developing and systematically studying biodegradable porous Si/polycaprolactone composite fibers with a focus on engineering scaffolds for nervous system repair. The research is pursued under 4 main thrusts: 1) fabricate aligned or randomly oriented porous Si nanoparticle/polycaprolactone composite nanofiber scaffolds and determine photoluminescent properties and degradation of the scaffolds; 2) functionalize the surface of the porous Si/polycarpolactone nanofiber composites to improve cellular attachment and growth (including -OH and peptide functionalization) 3) incorporate and monitor release of bioactive therapeutics from the nanofiber composites that target the PI3K/Akt signaling pathway to enhance neurite extension (i.e. nerve growth factor, PTEN siRNA, and PTEN inhibitor) and 4) determine ability of nanofibers to enhance neurite extension (dosal root ganglion neurons)in vitro. Three key innovations of this research are the use of an airbrush method to fabricate nanofiber composites, utilizing photolumiscent properties of porous Si nanoparticles to monitor degradation of the composite scaffolds, and incorporating sensitive therapeutics into nanofiber composites to enhance neurite extension. If successful, the approach will have applications in medical therapeutics, tissue engineering, and implantable scaffold imaging and broadly impact research areas of implantable biomaterials, MEMS, and controlled drug release. Students involved in the research will be provided with a highly interdisciplinary education in materials chemistry, nanoscience, biomedical engineering, and biology, in preparation for a variety of challenging research positions in the biotech sectors of industry, government, and academia. A capstone activity will be a 6-week summer school for silicon nanotechnology, involving high school, undergraduate, and graduate student mentors and mentees.

PI：Sailor，Michael J.提案编号：1603177纳米纤维支架已广泛用于神经再生策略；然而，当前的纳米纤维技术缺乏完全修复受损神经系统的能力，这通常是由于制造过程中使用的挥发性溶剂导致难以将敏感的治疗药物融入纳米纤维中。 该提案小组是第一个证明多孔硅纳米颗粒在体内降解为无毒硅酸副产物的团队，也是第一个证明纳米颗粒在体内使用门控发光成像可视化的能力的团队。 拟议研究的目标是在这些结果的基础上，将多孔硅纳米颗粒与聚己内酯纳米纤维的优点相结合，从而开发出药物释放复合纳米纤维，有助于增加神经突生长并改善神经系统修复。 纳米粒子为治疗提供保护，增强成像潜力，并可用于改变降解过程。 可以仔细控制排列的纳米纤维提供了再生基质，用于增强/引导延伸神经突的生长。 总之，如果成功，可生物降解的纳米纤维支架可以很容易地调整以改变支架降解率、光致发光强度、治疗递送和基质排列，将为开发下一代纳米纤维支架提供创新且简单的模型。参与研究的学生将接受材料化学、纳米科学、生物医学工程和生物学方面的高度跨学科教育。一项顶峰活动将是为期 6 周的硅纳米技术暑期学校，涉及高中生、本科生和研究生的导师和学员。纳米纤维支架已广泛用于神经再生策略；然而，当前的纳米纤维技术缺乏完全修复受损神经系统的能力，这通常是由于制造过程中使用的挥发性溶剂导致难以将敏感治疗剂（例如蛋白质、siRNA等）融入纳米纤维中。 这个为期三年的项目的目标是开发复合纳米纤维，其中可以纳入生物活性疗法，旨在创建用于神经系统修复的可定制组织工程支架。该提案小组是第一个证明多孔硅纳米颗粒在体内降解为无毒硅酸副产物的团队，也是第一个证明纳米颗粒在体内使用门控发光成像可视化的能力的团队。该提案的目标将通过开发和系统研究可生物降解的多孔硅/聚己内酯复合纤维来实现，重点是用于神经系统修复的工程支架。该研究主要围绕四个方向进行：1）制造定向或随机定向的多孔硅纳米颗粒/聚己内酯复合纳米纤维支架，并确定支架的光致发光性能和降解； 2) 功能化多孔 Si/聚碳内酯纳米纤维复合材料的表面，以改善细胞附着和生长（包括 -OH 和肽功能化） 3) 纳入并监测生物活性治疗剂从纳米纤维复合材料中的释放，这些药物靶向 PI3K/Akt 信号通路以增强神经突延伸（即神经生长因子、PTEN siRNA 和 PTEN 抑制剂）和 4) 确定纳米纤维在体外增强神经突延伸（背根神经节神经元）的能力。 这项研究的三个关键创新是使用喷枪方法制造纳米纤维复合材料，利用多孔硅纳米粒子的光致发光特性来监测复合支架的降解，以及将敏感治疗剂融入纳米纤维复合材料中以增强神经突延伸。 如果成功，该方法将应用于医学治疗、组织工程和植入式支架成像，并广泛影响植入式生物材料、MEMS 和受控药物释放的研究领域。 参与研究的学生将接受材料化学、纳米科学、生物医学工程和生物学等方面的高度跨学科教育，为工业界、政府和学术界生物技术领域各种具有挑战性的研究职位做好准备。一项顶峰活动将是为期 6 周的硅纳米技术暑期学校，涉及高中生、本科生和研究生的导师和学员。