Project Summary This R03 application aims to create innovative magnetically responsive drug delivery electrospun fibers to improve regeneration after spinal cord injury (SCI). Traumatic spinal cord injury (SCI) is a devastating condition currently affecting approximately 296,000 US citizens, with around 18,000 new cases each year. SCI occurs when a severe physical force causes compression of the spinal cord, killing neurons and glia at the injury site. Multiple secondary injury cascades are initiated immediately after the initial insult and lead to additional neuronal loss. The degree of inflammation that occurs after SCI has been shown to relate to the magnitude and duration of secondary injury. Depending on the severity of the SCI and the demographics of the patient, the inflammatory response varies after injury. Biomaterials, such as electrospun fibers, can provide local release of therapeutics to limit adverse off-target effects; however, drug-releasing biomaterials do not address the variability of patient inflammation. To provide a means of tailoring the therapeutic delivery to a patient, we propose to fabricate magnetic, growth factor-loaded coaxial electrospun fibers that can be stimulated non-invasively with a magnetic field to increase the rate of growth factor release from the fibers. Over the past several years, the Gilbert laboratory in collaboration with several other laboratories have applied superparamagnetic iron oxide nanoparticles (SPIONs) to astrocyte and neuronal cultures. More recently, our group has applied SPIONs to polymer systems, creating unique composites where magnetic fields can move aligned polymer fibers to more successfully direct extending neurites in culture. In collaboration with the Samuel laboratory, we were able to apply magnetic field stimulation to neurons cultured on scaffolds where SPIONs were tethered to fibrous scaffolds to stimulate neurite outgrowth. In this proposal, we hypothesize that the combination of SPIONs with electrospun fibers can create unique drug delivering scaffolds capable of releasing drugs at precise dosages that are tailored to a patient’s inflammatory response. Our group recently showed that the anti-inflammatory cytokine transforming growth factor beta 3 (TGFβ3) mitigates astrocyte reactivity in culture. Loading TGFβ3 into magnetic polymer fibers may allow for on-demand delivery of precise TGFβ3 dosages to mitigate astrocyte reactivity and more effectively treat an individual’s unique SCI. This project is likely to make significant contributions by developing new biomaterials capable of releasing large therapeutic molecules at precise dosages using an external magnetic field. Furthermore, approaches that focus on astrocyte phenotype may yield new areas of research where the astrocytes, not extending axons, are the focus of future treatments for SCI.