ab9b01012_si_001.pdf (220.78 kB)
PLG Bridge Implantation in Chronic SCI Promotes Axonal Elongation and Myelination
journal contribution
posted on 2019-11-13, 21:08 authored by Dominique
R. Smith, Courtney M. Dumont, Andrew J. Ciciriello, Amina Guo, Ravindra Tatineni, Mary K. Munsell, Brian J. Cummings, Aileen J. Anderson, Lonnie D. SheaSpinal 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) multichannel bridge implanted into a chronic
SCI following surgical resection of necrotic tissue. We characterized
the dynamic injury response and noted that scar formation decreased
at 4 and 8 weeks postinjury (wpi), yet macrophage infiltration increased
between 4 and 8 wpi. Subsequently, the scar tissue was resected and
bridges were implanted at 4 and 8 wpi. We observed robust axon growth
into the bridge and remyelination at 6 months after initial injury.
Axon densities were increased for 8 week bridge implantation relative
to 4 week bridge implantation, whereas greater myelination, particularly
by Schwann cells, was observed with 4 week bridge implantation. The
process of bridge implantation did not significantly decrease the
postinjury function. Collectively, this chronic model follows the
pathophysiology of human SCI, and bridge implantation allows for clear
demarcation of the 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.