title: Delivery of neurotrophin-3 from fibrin enhances neuronal fiber sprouting after spinal cord injury.
abstract: Neurotrophins have been shown to promote axonal growth and regeneration after spinal cord injury. The therapeutic utility of neurotrophins may be enhanced by using a controlled delivery system to increase the duration of neurotrophin availability following injury. Such a delivery system can be incorporated into a bioactive scaffold to serve as a physical bridge for regeneration. This study assessed the effect of controlled delivery of neurotrophin-3 (NT-3) from fibrin scaffolds implanted in spinal cord lesions immediately following 2-mm ablation injury in adult rats. Nine days after injury, fibrin scaffolds containing the delivery system and NT-3 (1000 ng/mL) elicited more robust neuronal fiber growth into the lesion than did control scaffolds or saline (1.5- to 3-fold increase). Implantation of fibrin scaffolds resulted in a dramatic reduction of glial scar formation at the white matter border of the lesion. Hindlimb motor function of treated animals did not improve relative to controls at 12 weeks post-injury. Thus, controlled delivery of NT-3 from fibrin scaffolds enhanced the initial regenerative response by increasing neuronal fiber sprouting and cell migration into the lesion, while functional motor recovery was not observed in this model.
authors.affiliation: Department of Biomedical Engineering, Washington University, St. Louis, MO 63130, USA.
authors.forename: Sara J
authors.initials: SJ
authors.lastname: Taylor
authors.forename: Ephron S
authors.initials: ES
authors.lastname: Rosenzweig
authors.forename: John W
authors.initials: JW
authors.lastname: McDonald
authors.forename: Shelly E
authors.initials: SE
authors.lastname: Sakiyama-Elbert
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000473:pathology; D002465:Cell Movement; D004195:Disease Models, Animal; D004337:Drug Carriers; D004343:Drug Implants; D005260:Female; D005337:Fibrin / Q000737:chemistry*; D006493:Heparin / Q000737:chemistry*; D017628:Microglia / Q000187:drug effects / Q000473:pathology; D009043:Motor Activity / Q000187:drug effects; D009412:Nerve Fibers / Q000145:classification / Q000187:drug effects* / Q000473:pathology; D009416:Nerve Regeneration; D020933:Neurotrophin 3 / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D020318:Rats, Long-Evans; D013116:Spinal Cord / Q000187:drug effects* / Q000473:pathology / Q000601:surgery; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000473:pathology
chemical_list: D004337:Drug Carriers; D004343:Drug Implants; D020933:Neurotrophin 3; D005337:Fibrin; D006493:Heparin