The 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.