title: Sustained release of neurotrophin-3 via calcium phosphate-coated sutures promotes axonal regeneration after spinal cord injury.
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. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Neurological Surgery, University of Wisconsin, Madison, Wisconsin.
authors.forename: Amgad
authors.initials: A
authors.lastname: Hanna
authors.affiliation: Department of Neurological Surgery, University of Wisconsin, Madison, Wisconsin.|Department of Biomedical Engineering, University of Wisconsin, Madison, Wisconsin.
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Thompson
authors.affiliation: Department of Neurological Surgery, University of Wisconsin, Madison, Wisconsin.|Department of Biomedical Engineering, University of Wisconsin, Madison, Wisconsin.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Hellenbrand
authors.affiliation: Department of Biomedical Engineering, University of Wisconsin, Madison, Wisconsin.|Department of Orthopedics and Rehabilitation, University of Wisconsin, Madison, Wisconsin.
authors.forename: Jae-Sung
authors.initials: JS
authors.lastname: Lee
authors.affiliation: Department of Neurological Surgery, University of Wisconsin, Madison, Wisconsin.
authors.forename: Casey J
authors.initials: CJ
authors.lastname: Madura
authors.affiliation: Department of Neurological Surgery, University of Wisconsin, Madison, Wisconsin.
authors.forename: Meredith G
authors.initials: MG
authors.lastname: Wesley
authors.affiliation: Department of Neurological Surgery, University of Wisconsin, Madison, Wisconsin.
authors.forename: Natalie J
authors.initials: NJ
authors.lastname: Dillon
authors.affiliation: Department of Neurological Surgery, University of Wisconsin, Madison, Wisconsin.
authors.forename: Tapan
authors.initials: T
authors.lastname: Sharma
authors.affiliation: Department of Neurological Surgery, University of Wisconsin, Madison, Wisconsin.
authors.forename: Connor J
authors.initials: CJ
authors.lastname: Enright
authors.affiliation: Department of Biomedical Engineering, University of Wisconsin, Madison, Wisconsin.|Department of Orthopedics and Rehabilitation, University of Wisconsin, Madison, Wisconsin.
authors.forename: William L
authors.initials: WL
authors.lastname: Murphy
mesh_terms: D000818:Animals; D001369:Axons / Q000187:drug effects*; D002130:Calcium Phosphates / Q000737:chemistry*; D002772:Cholera Toxin / Q000494:pharmacology; D003692:Delayed-Action Preparations; D005260:Female; D006085:Graft Survival / Q000187:drug effects; D009416:Nerve Regeneration / Q000187:drug effects*; D016900:Neurofilament Proteins / Q000378:metabolism; D020933:Neurotrophin 3 / Q000008:administration & dosage* / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function; D013119:Spinal Cord Injuries / Q000188:drug therapy / Q000628:therapy*; D013537:Sutures; D054457:Tissue Scaffolds
chemical_list: D002130:Calcium Phosphates; D003692:Delayed-Action Preparations; D016900:Neurofilament Proteins; D020933:Neurotrophin 3; D002772:Cholera Toxin
keywords: RRID:AB_2532999; RRID:AB_2535788; RRID:AB_641021; calcium phosphate coating; neurotrophin-3; peripheral nerve grafts; regeneration