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J Neurosci Res. 2016 Jul;94(7):645-52. doi: 10.1002/jnr.23730. Epub 2016 Mar 26.

Sustained release of neurotrophin-3 via calcium phosphate-coated sutures promotes axonal regeneration after spinal cord injury.

Author information

1
Department of Neurological Surgery, University of Wisconsin, Madison, Wisconsin.
2
Department of Biomedical Engineering, University of Wisconsin, Madison, Wisconsin.
3
Department of Orthopedics and Rehabilitation, University of Wisconsin, Madison, Wisconsin.

Abstract

Because of the dynamics of spinal cord injury (SCI), the optimal treatment will almost certainly be a combination approach to control the environment and promote axonal growth. This study uses peripheral nerve grafts (PNGs) as scaffolds for axonal growth while delivering neurotrophin-3 (NT-3) via calcium phosphate (CaP) coatings on surgical sutures. CaP coating was grown on sutures, and NT-3 binding and release were characterized in vitro. Then, the NT-3-loaded sutures were tested in a complete SCI model. Rats were analyzed for functional improvement and axonal growth into the grafts. The CaP-coated sutures exhibited a burst release of NT-3, followed by a sustained release for at least 20 days. Functionally, the rats with PNGs + NT-3-loaded sutures and the rats treated with PNGs scored significantly higher than controls on day 56 postoperatively. However, functional scores in rats treated with PNGs + NT-3-loaded suture were not significantly different from those of rats treated with PNGs alone. Cholera toxin subunit B (CTB) labeling rostral to the graft was not observed in any controls, but CTB labeling rostral to the graft was observed in almost all rats that had had a PNG. Neurofilament labeling on transverse sections of the graft revealed that the rats treated with the NT-3-loaded sutures had significantly more axons per graft than rats treated with an NT-3 injection and rats without NT-3. These data demonstrate that PNGs serve as scaffolds for axonal growth after SCI and that CaP-coated sutures can efficiently release NT-3 to increase axonal regeneration.

KEYWORDS:

RRID:AB_2532999; RRID:AB_2535788; RRID:AB_641021; calcium phosphate coating; neurotrophin-3; peripheral nerve grafts; regeneration

PMID:
27015737
DOI:
10.1002/jnr.23730
[Indexed for MEDLINE]

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