Biomaterial bridges enable regeneration and re-entry of corticospinal tract axons into the caudal spinal cord after SCI: association with recovery of forelimb function

Biomaterials, 2015 · DOI: 10.1016/j.biomaterials.2015.05.032 · Published: October 1, 2015

Simple Explanation

This study investigates a biodegradable implant using poly(lactideco-glycolide) (PLG) bridges as a carrier scaffold to support regeneration after spinal cord injury. The study used Crym:GFP transgenic mice to detect regeneration of descending neuronal tracts into the bridge, and beyond into intact caudal parenchyma. The key finding is that axons originating from descending fiber tracts regenerated, entered into the PLG bridge, continued through the bridge site, and exited to re-enter host tissue.

Study Duration

10 weeks

Participants

5 Crym:GFP C57Bl6 mice (PLG bridge), 5 control C57Bl6 mice (gelfoam)

Evidence Level

Not specified

Key Findings

1
Robust co-localization between GFP and neurofilament-200 (NF-200) as well as GFP and GAP-43 was observed at both the rostral and caudal bridge/tissue interface.
2
A significant increase in NF-200 labeling was found in bridge-implanted animals in both regions, suggesting axonal preservation adjacent to the site of bridge implantation and/or regeneration both into and out of the bridge in this cervical implantation model.
3
Regeneration through implanted bridges was associated with a reduction in ipsilateral forelimb errors on a horizontal ladder task.

Research Summary

This study describes a biodegradable implant using poly(lactideco-glycolide) (PLG) bridges as a carrier scaffold to support regeneration after injury. Taken together, these data suggest that axons originating from descending fiber tracts regenerated, entered into the PLG bridge at the rostral margin, continued through the bridge site, and exited to re-enter host tissue at the caudal edge of the intact bridge. Finally, regeneration through implanted bridges was associated with a reduction in ipsilateral forelimb errors on a horizontal ladder task.

Practical Implications

Promoting Axonal Regeneration

PLG bridges can create a permissive environment for axon regeneration that could support growth not only into the biomaterial channels, but enable re-entry of regenerated descending fibers into intact spinal cord parenchyma caudal to the implant.

Functional Motor Recovery

PLG bridges can lead to functional motor recovery in an SCI model in comparison with no-bridge control conditions in the absence of exogenous cells or trophic factors.

Clinical Relevance for SCI

The potential of an implanted bridge alone, that is, without combination with trophic factors or seeded cell populations, to promote both regeneration and recovery of function is both novel and clinically relevant for SCI.

Study Limitations

1
The potential contribution of minimization of tissue loss and glial scar formation cannot be excluded.
2
Further studies investigating the mechanisms of recovery, including the establishment of direct evidence of synaptic/functional connectivity, are necessary.
3
The potential contribution of other descending tracts to spinal cord GFP reporter labeling is not excluded.

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