Abstract
Positively-charged oligo[poly(ethylene glycol)fumarate] (OPF+) is a biodegradable hydrogel used for spinal cord injury repair. We compared scaffolds containing primary Schwann cells (SCs) to scaffolds delivering SCs genetically modified to secrete high concentrations of glial cell-derived neurotrophic factor (GDNF). Multichannel OPF+ scaffolds loaded with SCs or GDNF-SCs were implanted into transected rat spinal cords for 4 weeks. GDNF-SCs promoted regeneration of more axons into OPF+ scaffolds (2773.0 ± 396.0) than primary SC OPF+ scaffolds (1666.0 ± 352.2) (p = 0.0491). This increase was most significant in central and ventral-midline channels of the scaffold. Axonal remyelination was quantitated by stereologic analysis. Increased myelination of regenerating axons was observed in the GDNF-SC group. Myelinating cell and axon complexes were formed by host SCs and not by implanted cells or host oligodendrocytes. Fast Blue retrograde tracing studies determined the rostral-caudal directionality of axonal growth. The number of neurons that projected axons rostrally through the GDNF-SC scaffolds was higher (7929 ± 1670) than in animals with SC OPF+ scaffolds (1069 ± 241.5) (p < 0.0001). The majority of ascending axons were derived from neurons located more than 15 mm from the scaffold-cord interface, and were identified to be lumbosacral intraspinal motor neurons. Transected animals with GDNF-SC OPF+ scaffolds partially recovered locomotor function at weeks 3 and 4 following surgery.
Original language | English (US) |
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Pages (from-to) | e398-e407 |
Journal | Journal of Tissue Engineering and Regenerative Medicine |
Volume | 12 |
Issue number | 1 |
DOIs | |
State | Published - Jan 2018 |
Keywords
- Schwann cells
- glial-derived neurotrophic factor
- hydrogel
- oligo[poly(ethylene glycol)fumarate]
- scaffolds
- spinal cord injury
ASJC Scopus subject areas
- Medicine (miscellaneous)
- Biomaterials
- Biomedical Engineering