Porous Silicon Nanoparticle/Polycaprolactone Composite Nanofibers for Nervous System Repair

p: Sailor, Michael j .纳米纤维支架在神经再生策略中的广泛应用；然而，目前的纳米纤维技术缺乏完全修复受损神经系统的能力，这通常是由于制造纳米纤维时使用的挥发性溶剂导致难以将敏感治疗药物纳入纳米纤维。该研究小组首先证明了多孔硅纳米颗粒在体内降解为无毒的硅酸副产物，并首次证明了纳米颗粒在体内使用门控发光成像的可视化能力。本研究的目标是将多孔硅纳米颗粒与聚己内酯纳米纤维的优势结合起来，从而开发出能够帮助增加神经突生长和改善神经系统修复的药物释放复合纳米纤维。纳米颗粒为治疗提供保护，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，生物可降解的纳米纤维支架可以很容易地调整支架的降解速率、光致发光强度、治疗递送和底物排列，将为开发下一代纳米纤维支架提供一个创新和直接的模型。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等高度跨学科的教育。一个顶点活动将是为期六周的硅纳米技术暑期学校，包括高中生、本科生和研究生的导师和指导者。纳米纤维支架已广泛应用于神经再生策略；然而，目前的纳米纤维技术缺乏完全修复受损神经系统的能力，这通常是由于制造纳米纤维时使用的挥发性溶剂导致难以将敏感疗法（如蛋白质、siRNA等）纳入纳米纤维。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治疗，目的是为神经系统修复创造可定制的组织工程支架。该研究小组首次证明了多孔硅纳米颗粒在体内降解为无毒的硅酸副产物，并首次证明了纳米颗粒在体内使用门控发光成像的可视化能力。本课题的目标是开发和系统研究可生物降解多孔硅/聚己内酯复合纤维，重点研究用于神经系统修复的工程支架。主要研究方向为：1)制备排列或随机取向多孔硅纳米颗粒/聚己内酯复合纳米纤维支架，并测定其光致发光性能和降解性能；2)功能化多孔硅/聚碳内酯纳米纤维复合材料的表面，以改善细胞的附着和生长（包括-OH和肽功能化）3)结合并监测纳米纤维复合材料中生物活性药物的释放，这些药物靶向PI3K/Akt信号通路，以增强神经突起的延伸(如神经生长因子，PTEN siRNA，以及PTEN抑制剂)和4)测定纳米纤维增强神经突延伸（剂量根神经节神经元）的能力。本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，利用多孔硅纳米颗粒的光致发光特性来监测复合材料支架的降解，以及将敏感疗法纳入纳米纤维复合材料以增强神经突的延伸。如果成功，该方法将应用于医学治疗、组织工程、可植入支架成像，并广泛影响可植入生物材料、MEMS和药物控制释放等研究领域。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等高度跨学科的教育，为在工业、政府和学术界的生物技术部门担任各种具有挑战性的研究职位做好准备。一个顶点活动将是为期六周的硅纳米技术暑期学校，包括高中生、本科生和研究生的导师和指导者。

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.