Bossone Research Center, Room 302, located at 32nd and Market Streets.
BIOMED PhD Research Proposal
A Multifaceted Approach to Promote Neuronal Growth after Spinal Cord Injury
Brian Oeffinger, PhD Candidate, School of Biomedical Engineering, Science and Health Systems, Drexel University
Margaret Wheatley, PhD, John M. Reid Professor, School of Biomedical Engineering, Science and Health Systems, Drexel University
Spinal cord injury (SCI) repair is impeded by both the poor regenerative capacity of adult spinal cord and the formation of inhibitory scar tissue around a large cystic lesion. A successful healing strategy must simultaneously overcome the negative cues from the scar while providing positive cues to allow axons to grow across the lesion to connect with their targets. Our long-term goal is to develop a multi-component biocompatible platform that will enable a diversity of synergistic healing strategies at the site of SCI. The strategy includes a novel ultrasound based system for targeted, timed delivery of small interfering RNA (siRNA) and a multifunctional biopolymer scaffold that provides both structural support with spatial and temporal chemical cues to actively assist in regeneration.
The unique interactions between ultrasound and microbubbles (MB) will be employed for targeted, timed delivery of siRNA to prevent over-expression of inhibitory proteins, focusing on RhoA, that prevent neurite repair and growth. Delivery to the SCI site will be achieved by loading siRNA onto polymer MB, injecting the MB into the cerebrospinal fluid, and triggering controlled release using ultrasound. To provide positive cues to promote axon growth, a three-dimensional, directionally frozen chitosan-alginate polyelectrolyte complex platform will be functionalized with immobilized growth factor gradients. Together, the individual components of the proposed systems are expected to have a synergistic effect on repair, re-growth and re-establishment of function, overcoming the many barriers to successful SCI repair.