BMEGSA Midwest Student Speaker Exchange: Dominique Smith, University of Michigan

Graduate Research Fellow, Department of Biomedical Engineering, University of Michigan

Abstract: 

"PLG bridge implantation in chronic SCI promotes axonal regeneration"

Spinal cord injury (SCI) is a devastating condition that may cause permanent functional loss below the level of injury, including paralysis and loss of bladder, bowel, and sexual function. Patients are rarely treated immediately, and this delay is associated with tissue loss and scar formation that can make regeneration at chronic time points more challenging. Herein, we investigated regeneration using a poly(lactide-co-glycolide) (PLG) multi-channel bridge, which has previously been used in acute SCI models, implanted into a chronic SCI following surgical resection of necrotic tissue. We initially characterized the dynamic injury response and noted that scar formation decreased at 4 and 8 weeks post injury (wpi), yet macrophage infiltration increased between 4 and 8 wpi. Subsequently, scar tissue was resected and bridges implanted at 4 and 8 wpi. Bridge implantation did not exacerbate functional deficits; however, while robust axon growth into the bridge and myelination were observed with implantation at both time points, no recovery of function was observed. Axon densities were increased for bridge implantation at 8 weeks relative to 4 weeks, whereas greater myelination, particularly by Schwann cells, was observed with bridge implantation at 4 weeks. Collectively, this chronic model follows the pathophysiology of human SCI and bridge implantation allows for clear demarcation of regenerated tissue. These data demonstrate that bridge implantation into chronic SCI supports regeneration and provides a platform to investigate strategies to buttress and expand regeneration of neural tissue at chronic time points.