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.

主要研究者：Sailor，Michael J.Proposal #：1603177纳米纤维支架已被广泛用于神经再生策略;然而，目前的神经再生技术缺乏完全修复受损神经系统的能力，这通常是由于难以将敏感的治疗剂纳入由其制造中使用的挥发性溶剂引起的纳米纤维中。 提出小组是第一个证明多孔硅纳米颗粒在体内降解为无毒的草酸副产物的小组，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小组。 拟议研究的目标是通过将多孔硅纳米颗粒与聚己内酯纳米纤维的优势相结合来建立这些结果，从而开发药物释放复合纳米纤维，可以帮助增加神经突生长和改善神经系统修复。 纳米颗粒提供治疗剂的保护，增强成像潜力，并可用于改变降解过程。 纳米纤维的排列可以被仔细控制，提供了一种再生基质，用于增强/指导延伸神经突的生长。 总之，如果成功的话，可生物降解的生物可降解支架，可以很容易地调整，以改变支架降解速率，光致发光强度，治疗输送和基板对齐，将提供一个创新的和简单的模型，用于开发下一代的生物可降解支架。参与研究的学生将获得材料化学，纳米科学，生物医学工程和生物学方面的高度跨学科教育。一个顶点活动将是一个为期6周的硅纳米技术暑期学校，涉及高中，本科和研究生导师和学员。纳米纤维支架已被广泛用于神经再生策略;然而，目前的神经再生技术缺乏完全修复受损神经系统的能力，这通常是由于难以将敏感的治疗剂（如蛋白质、siRNA等）掺入纳米纤维中，这是由其制造中使用的挥发性溶剂引起的。 这个为期三年的项目的目标是开发复合纳米纤维，其中可以包含生物活性治疗剂，目的是为神经系统修复创建可定制的组织工程支架。提出小组是第一个证明多孔硅纳米颗粒在体内降解为无毒的草酸副产物的小组，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小组。本研究的目的是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，重点是神经系统修复的工程支架。本论文的主要研究内容包括：1）制备有序或无规取向的多孔硅纳米粒子/聚己内酯复合纳米支架，并测定其光致发光性能和降解性能; 2）对多孔硅/聚己内酯复合材料表面进行功能化处理，以改善细胞的附着和生长（包括-OH和肽功能化）3）掺入并监测生物活性治疗剂从靶向PI 3 K/Akt信号传导途径以增强神经突延伸的生物活性复合物的释放（即神经生长因子、PTEN siRNA和PTEN抑制剂）和4）测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神经纤维复合材料，利用多孔硅纳米颗粒的光致发光特性来监测复合材料支架的降解，并将敏感的治疗剂纳入神经纤维复合材料以增强神经突延伸。 如果成功，该方法将应用于医疗治疗，组织工程和可植入支架成像，并广泛影响可植入生物材料，MEMS和药物控释的研究领域。 参与研究的学生将获得材料化学，纳米科学，生物医学工程和生物学方面的高度跨学科教育，为工业，政府和学术界生物技术部门的各种具有挑战性的研究职位做准备。一个顶点活动将是一个为期6周的硅纳米技术暑期学校，涉及高中，本科和研究生导师和学员。