Effect of hierarchically aligned fibrin hydrogel in regeneration of spinal cord injury demonstrated by tractography: A pilot study

Zhenxia Zhang,Jun Fu,Xiumei Wang,Jingming Wang,Feiyan Chang,Shenglian Yao,Jie Luo,Sheng Xie

doi:10.1038/srep40017

Abstract

Some studies have reported that scaffold or cell-based transplantation may improve functional recovery following SCI, but no imaging information regarding regeneration has been provided to date. This study used tractography to show the regenerating process induced by a new biomaterial-aligned fibrin hydrogel (AFG). A total of eight canines subjected to SCI procedures were assigned to the control or the AFG group. AFG was implanted into the SCI lesion immediately after injury in 5 canines. A follow-up was performed at 12 weeks to evaluate the therapeutic effect including the hindlimb functional recovery, anisotropy and continuity of fibers on tractography. Using tractography, we found new fibers running across the SCI in three canines of the AFG group. Further histological examination confirmed limited glial scarring and regenerated nerve fibers in the lesions. Moreover, Repeated Measures Analysis revealed a significantly different change in fractional anisotropy (FA) between the two groups during the follow-up interval. An increase in FA during the post injury time interval was detected in the AFG group, indicating a beneficial effect of AFG in the rehabilitation of injured axons. Using tractography, AFG was suggested to be helpful in the restoration of fibers in SCI lesions, thus leading to promoted functional recovery.

Highlights

The locomotion and functional sensory recovery on completely transected spinal cord injuries (SCI) models, rendering some canines capable of standing unassisted and transiently moving
As confirmed by histological observation, the effects of therapy with aligned fibrin hydrogels (AFG) implantation into the spinal cord were demonstrated in the canine SCI models using tractography
Regeneration of nerve fibers was detected on histological sections, which was in agreement with the reconstruction of fibers in the hemisection side on tractography

Summary

Introduction

The locomotion and functional sensory recovery on completely transected SCI models, rendering some canines capable of standing unassisted and transiently moving. Their histological analysis showed that administration of biomaterial implants reduced lesion volume, decreased collagen deposits, promoted axon regeneration and improved myelination[5]. DTI with subsequent fiber tracking is capable of visualizing the white matter, and this technical advancement enables the reconstruction of white matter tracts in 3D view, of the brain and of the spinal cord. DTI tractography can be used as a qualitative indicator of SCI to track the damaged nerve fibers visually and clearly observe the axonal bundles lesion[9,11,12,13]. Our hypothesis is that the AFG may exert great effects on the recovery of spinal cord white matter injury and that DTI can provide information statistically and visually to assess the integrity of spinal cord fibers, which would be in line with histopathologic results

Methods

Results

Conclusion