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

1134119/1134449刘/曹该奖项的研究目标是开发一种新技术，利用神经干细胞(NSCs)作为脊髓损伤(SCI)修复的构建块，制造可注射、可对准和具有生物活性的支架。这项工作利用了远程和非侵入性地操纵超顺磁性氧化铁纳米颗粒(SPION)的能力。在这种方法中，神经干细胞被包裹了大量SPION的纳米工程阳离子磁脂质体(CMLS)标记，并以胶体悬浮液的形式注射到损伤的脊髓中。当施加磁场时，磁性标记的神经干细胞将自发地自组装成链状/柱状晶格，并沿着由磁场磁通线定义的虚拟轴排列，从而形成引导轴突定向再生的支架。射频电磁触发可以释放储存在CMLS双层中的神经营养因子，从而促进NSC的存活和轴突生长。如果成功，这项研究将改变组织工程中生物支架制造的最先进水平，当需要定向指导细胞生长和扩张时，并加强对实验性脊髓损伤和神经退行性疾病的挑战性问题的治疗策略。这项工作还将有助于通过将SPION的作用从被动示踪剂(例如磁共振成像(MRI)造影剂)转变为生物过程的主动使能器，从而大大扩大SPION在一般临床应用中的使用。开发的技术可以方便地转化为各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。它将使数十万因这些疾病而行动严重受限或瘫痪的美国人受益。此外，这项工作研究了在组织学条件下软生物颗粒的磁定向自组装，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，这构成了各种微/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方案，通过积极招收合格的少数族裔学生进行本科生和研究生学习以及参与K-12教师/学生外联活动，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.