Collaborative Research: Magnetic Directed Alignment of Injectable Neural Stem Cell Scaffold for Regeneration After Spinal Cord Injury

刘/曹本奖项的研究目标是开发一种以神经干细胞（NSCs）为基础材料，制造可注射、可对齐、具有生物活性的脊髓损伤修复支架的新技术。这项工作利用了超顺磁性氧化铁纳米颗粒（SPIONs）的远程、无创磁场操纵能力。在这种方法中，NSCs被纳米工程阳离子磁性脂质体（cml）标记，cml包裹了许多SPIONs，可以以胶体悬浮液的形式注射到受损的脊髓中。当施加磁场时，磁性标记的NSCs会自发地自组装成链/柱晶格，并沿着由磁场通量线定义的虚拟轴排列，从而形成一个支架来引导轴突的定向再生。储存在cml双分子层的神经营养因子可通过射频电磁触发释放，促进NSC存活和轴突生长。如果成功，本研究将改变组织工程中生物支架制造的最新技术，当细胞生长和扩增需要定向指导时，并增强实验性脊髓损伤和神经退行性疾病挑战性问题的治疗策略。通过将SPIONs的作用从被动示踪剂（如磁共振成像造影剂）转变为生物过程的主动推动者，这项工作还将有助于极大地扩大SPIONs在一般临床应用中的应用。所开发的技术可以方便地转化为多种神经系统疾病的临床治疗，如创伤性脑损伤（TBI）和周围神经疾病。它将使成千上万的行动能力严重受限或因这些疾病而瘫痪的美国人受益。此外，本研究还研究了软性生物颗粒在组织学条件下的磁定向自组装，这些发现将促进对偶极胶体中聚集动力学和相分离的基本理解，这是各种微/纳米流体应用的基础。通过拟议的项目，将建立一个综合的跨学科研究和教育计划，通过积极招收合格的少数民族学生进行本科和研究生学习，并通过参与K-12教师/学生外展活动，为代表性不足的群体创造大量机会。

1134119 / 1134449Liu / CaoThe research objective of this award is to develop a novel technique to fabricate injectable, alignable, and bioactive scaffold that uses neural stem cells (NSCs) as building blocks for spinal cord injury (SCI) repair. This work capitalizes on the ability to manipulate superparamagnetic iron oxide nanoparticles (SPIONs) with magnetic field remotely and noninvasively. In this approach, the NSCs are labeled with nanoengineered cationic magnetoliposomes (CMLs) which encapsulate numerous SPIONs, and can be injected into the injured spinal cord in colloidal suspensions. Upon the application of a magnetic field, magnetically labeled NSCs will spontaneously self-assemble into chain/column lattices and align along a virtual axis that is defined by the field flux lines, thereby forming a scaffold to guide the directional regrowth of axons. Neurotrophic factors stored in the bilayer of the CMLs can be released by radio frequency electromagnetic triggering to promote NSC survival and axonal growth. If successful, this research will transform state-of-the-art of biological scaffold fabrication in tissue engineering, when directional guidance is desired for cellular growth and expansion, and enhance the therapeutic strategies for challenging issues of experimental spinal cord injury and neurodegenerative diseases. This work will also help to greatly expand the use of SPIONs in general clinical applications by changing their role from passive tracer (e.g., magnetic resonance imaging (MRI) contrast agents) to active enabler of biological processes. The technology developed can be conveniently translated to clinical treatments of a diverse group of nervous system diseases, such as traumatic brain injury (TBI) and peripheral nerve disorders. It will benefit hundreds of thousands of Americans who are have severely limited mobility or paralyzed incurring from these diseases. Additionally, this work investigates the magnetic directed self-assembly of soft biological particles under histological conditions, and the findings will advance fundamental understanding of aggregation kinetics and phase separation in dipolar colloids, which constitutes the basis of a variety of micro/nanofluidic applications. Through the proposed project, an integrated interdisciplinary research and education program will be established which creates vast opportunities for underrepresented groups, by actively recruiting qualified minority students for both undergraduate and graduate studies and by engaging in K-12 teacher/student outreach activities.